Waa maxay Sulforaphane?

Sulforaphane waa phytochemical , walax ka tirsan kooxda isothiocyanate ee xeryahooda organosulfur, laga helo khudaarta cruciferous, sida brokoli, kaabajka, cauliflower, iyo sprouts Brussels. Waxa kale oo laga heli karaa bok choy, kale, collars, cagaarka iniin khardal ah iyo watercress. Cilmi baaris ayaa muujisay in sulforaphane ay ka caawin karto ka hortagga noocyada kala duwan ee kansarka kicinta wax soo saarka Nrf2, ama xuubka nukliyeerka erythroid 2- la xidhiidha, cunsur qoraal ah oo nidaamiya hababka difaaca jirka ee xakameynaya jawaabta unugga ee oksaydhiyeyaasha. Ujeedada maqaalkan soo socda waa in lagu qeexo shaqada sulforaphane.

aan la taaban karin

Nidaamka antioxidant KEAP1-Nrf2-ARE waa macne muhiim ah oo unugyadu ay uga jawaabaan cadaadiska oksaydhka iyo xenobiotic. Sulforaphane (SFN), isothiocyanate electrophilic oo ka soo jeeda khudaarta cruciferous, waxay kicisaa waddada KEAP1-Nrf2-ARE waxayna noqotay molecule-xiisaha daaweynta cudurrada kaas oo diiqada oksaydhka ee daba-dheeraada ay door weyn ka qaadato etiological. Waxaan halkan ku muujineynaa in mitochondria ee dhaqameed, unugyada midabka isha ee bini'aadamka ee epithelial (RPE-1) ee lagu daaweeyay SFN ay maraan hyperfusion taas oo ka madax bannaan labadaba Nrf2 iyo cytoplasmic inhibitor KEAP1. Fududeynta Mitochondrial ayaa lagu soo warramey inay tahay cytoprotective iyadoo la xakameynayo sameynta pore ee mitochondria inta lagu jiro apoptosis, oo taas la socota, waxaan muujineynaa Nrf2-madax banaan, cytoprotection ee unugyada SFN-la daaweeyay ee soo gaadhay apoptosis-inducer, staurosporine. Farsamo ahaan, SFN waxay yaraynaysaa qoritaanka iyo/ama sii haynta fayraska fissionka ah ee Drp1 ilaa mitochondria iyo peroxisomes laakiin ma saamayso guud ahaan badnaanta Drp1. Xogtaasi waxay muujinaysaa in sifooyinka faa'iidada leh ee SFN ay ka sii dheer yihiin firfircoonida nidaamka KEAP1-Nrf2-ARE waxayna dammaanad qaadayaan su'aalo dheeraad ah oo la siiyay isticmaalka hadda ee wakiilkan ee tijaabooyin badan oo caafimaad.

Keywords: Sulforaphane, Nrf2, Drp1, Mitochondria, Fission, Fusion, Apoptosis

Hordhac

Sulforaphane waa Nrf2-Inhibitor Madax-bannaan ee Mitochondrial Fission

Sulforaphane (SFN) waa iskudhis isothiocyanate oo ka soo jeeda cuntada inta badan laga helo khudaarta cruciferous [56]. Waxaa lagu soo saaraa dhirta sida jawaabta xenobiotic ee ugaadhsiga iyada oo loo marayo sii-deynta vesicular ee myrosinase hydrolytic enzyme ka unugyada dhaawacan; Enzyme-gani wuxuu u beddelaa glucosinolates ilaa isothiocyantes [42]. Labaatankii sano ee la soo dhaafay, SFN waxaa si weyn loogu asteeyay ka hortagga kansarka, antioxidant, iyo guryaha antimicrobial [57]. Inta badan waxtarkan waxaa loo aaneynayaa awoodda SFN si loo beddelo habka KEAP1-Nrf2-antioxidant element (ARE), inkasta oo waxqabadyada dheeraadka ah ee xarunta la aqoonsaday, oo ay ku jiraan joojinta dhaqdhaqaaqa histone deacetylase iyo horumarka wareegga unugyada. 29]. Nrf2 waa qodobka ugu muhiimsan ee qoraalka antioxidant iyo xaaladaha homeostasis, xasiloonida waxaa lagu xakameynayaa ficilka cytoplasmic Cullin3KEAP1 ubiquitin ligase complex [20]. Gaar ahaan, Nrf2 waxaa lagu shaqaaleysiiyay cullin3KEAP1 ligase iyadoo lagu xirayo adabtarada substrate-ka dimeric KEAP1 ka dibna waxaa lagu beddelay silsilado polyUb kuwaas oo bartilmaameedsanaya qodobka qoraalka ee hoos u dhaca dhexdhexaadinta boroteasome. Isbeddelkan ka kooban yahay wuxuu xaddidaa nolosha nuska ah ee Nrf2 ee unugyada aan cadaadiska lahayn ilaa ~ 15 min [30], [33], [46], [55]. Iyada oo laga jawaabayo noocyo badan oo walbahaar ah, gaar ahaan cadaadiska oksaydhka, KEAP1, borotiinka hodanka ku ah cysteine, wuxuu u dhaqmaa sidii dareemayaal redox ah, iyo wax ka beddelka oksijiinta ee cysteins-ka muhiimka ah, gaar ahaan C151, ee KEAP1 waxay kala saartaa Nrf2-KEAP1 ee CUL3 taas oo ka hortagaysa hoos u dhaca Nrf2. 8], [20], [55]. Gaar ahaan, SFN, iyo suurtogalnimada kuwa kale ee Nrf2 activators, waxay ku ekaysiiyaan diiqada oksaydhka iyagoo wax ka beddelaya C151 ee KEAP1 tusaale [21]. Xasilinta Nrf2 waxay u oggolaaneysaa in loo beddelo xuddunta halkaasoo ay ku keento muujinta baytariga Wajiga II ee antioxidant-ka iyo hiddo-wadaha sunta. Nrf2 waxay ku xidhan tahay walxaha dhiirrigeliyaha jawaab-celinta antioxidant (ARE) ee hiddo-wadaha bartilmaameedka ah iyada oo loo marayo heterodimerization oo leh borotiinno Maf yar yar [19]. Nidaamkani wuxuu soo bandhigayaa jawaab celin firfircoon oo xasaasi ah oo ku saabsan antioxidants aan toos ahayn sida SFN, xagjirnimada bilaashka ah ee ay dhaliso mitochondria [16], ama ilo kale oo nafsi ah oo cadaadis oksaydh ah [41].

Mitochondria waa firfircooni, unugyo-hoosaadyada hoose ee xakameynaya hawl-qabadyo badan oo unugyo ah oo u dhexeeya wax soo saarka ATP iyo kaalshiyamka kalsiyumka intracellular buffering si nidaaminta redox iyo apoptosis [13], [49]. Mitochondria waxay sidoo kale ka dhigan tahay isha ugu muhiimsan ee noocyada ogsijiinta falcelinta (ROS) ee unugyada. Nidaaminta saxda ah ee shaqada mitochondrial ayaa sidaas darteed lagama maarmaan u ah hagaajinta wax soo saarka ATP si loo daboolo baahiyaha gacanta iyadoo isla mar ahaantaana la yareynayo waxyeelada suurtagalka ah ee wax soo saarka xagjirnimada bilaashka ah. Baahida muhiimka ah ee habaynta wanaagsan ee shaqada mitochondrial waa awooda mitochondria si ay ugu shaqeyso labadaba si madax banaan sida mashiinada biochemical iyo iyada oo qayb ka ah shabakad ballaadhan, jawaab celin ah.

Shabakadda Mitochondrial morphology iyo shaqada waxaa lagu go'aamiyaa dheelitirnaanta la habeeyey ee u dhexeeya fiyuuska iyo fiyuuska. Mitochondrial fission ayaa looga baahan yahay dhaxalka unugyada gabadha mitochondria inta lagu jiro qaybta unugga [28] iyo sidoo kale xulashada, hoos u dhigista autophagic ee mitochondria ba'an ama dhaawacan, oo loo yaqaan mitophagy [1]. Taa beddelkeeda, fiyuuska ayaa looga baahan yahay dhammaystirka genome-ga mitochondrial iyo wadaagga qaybaha silsiladda gaadiidka elektaroonigga ah ee u dhexeeya mitochondria deriska ah [54]. Marka la eego heerka molecular, mitochondrial fission iyo fusion waxaa lagu nidaamiyaa GTPases waaweyn, dynamin u eg. Saddex enzymes ayaa ugu horreyn nidaamiya fiyuuska: Mitofusins ​​1 iyo 2 (Mfn1/2) waa borotiinno xuub-baxa ah oo dhexdhexaadiya xuubka dibadda ee isdhexgalka iyada oo loo marayo isdhexgalka heterotypic ee u dhexeeya mitochondria ku xiga [15], [25], [37], halka OPA1 uu yahay gudaha gudaha. borotiinka xuubabka kaas oo isku mar xaqiijiya isku xidhka matrixka isagoo nidaaminaya dhalaalka xuubabka gudaha [5]. Dhaqdhaqaaqa GTPase ee dhammaan saddexda borotiinada ayaa looga baahan yahay fiyuus adag [5], [18], iyo OPA1 waxaa lagu sii habeeyaa borotiinka adag ee gudaha xuubka gudaha ee mitochondrial by proteases OMA1 [14], PARL [6], iyo YME1L [45] ]. Muhiimad ahaan, awoodda xuubabka mitochondrial ee sugan ayaa looga baahan yahay fiyuus hufan si loo xakameeyo isdhexgalka mitochondria ee dhaawacan iyo caafimaadka qaba [26].

Mitochondrial fission ugu horrayn waxaa katalyeeyay borotiinka cytosolic ee loo yaqaan Dynamin-related protein 1 (Drp1/DNM1L). Drp1 waxaa laga qorayaa cytosol ilaa meelaha la filayo ee fiix ee xuubabka sare ee mitirka [43]. Soo-dhoweeyayaasha ugu waaweyn ee Drp1 ee xuubka sare waa mitochondrial fission factor (Mff) [32] iyo, ilaa xad, Fission 1 (Fis1) [51]. Intaa waxaa dheer, soo-dhoweeye decoy, MIEF1/MiD51, ayaa la ogaaday inuu u dhaqmo si uu u xaddido dhaqdhaqaaqa borotiinka Drp1 ee meelaha suurtagalka ah ee fission [58]. Marka lagu xidho xuubka sare ee mitochondrial, Drp1 oligomerizes qaab dhismeedyo u eg agagaarka jidhka mitochondrion ka dibna ka faa'iidaysta tamarta ka soo jeeda GTP hydrolysis si ay u dhexdhexaadiso maqaarka jirka ee xuubka mitirka gudaha iyo dibadda [17]. Tubooyinka Endoplasmic reticulum-ka soo jeeda waxay u dhaqmaan sidii curiyaha bilowga ah ee mitochondria ka hor Drp1 oligomerization, isagoo hoosta ka xariiqaya muujinta in mitochondria aan ciriiri lahayn ay ka ballaaran tahay wareegga oggolaanshaha ee Drp1 spiral [12]. Dhaqdhaqaaqa Actin ayaa sidoo kale muhiim u ah isdhexgalka ER-mitochondria ee ka horeeya fission mitirka [24]. Marka lagu daro doorkeeda fiisigga mitochondrial, Drp1 waxay kicisaa fission-ka peroxisomes [40].

Drp1 wuxuu aad ugu eg yahay borotiinka dynamin-ka ee si wanaagsan loo sifeeyay in labada borotiina ay ku jiraan N-terminal GTPase domain, oo ah meel dhexe oo muhiim u ah is-oligomerization, iyo C-terminal GTPase domain [31]. Drp1 waxay ku guulaysataa xulashada xuubabka mitochondrial iyada oo loo marayo isku-dhafka isdhexgalka ee borotiinnada soo-dhoweeyaha Mff iyo Fis1 iyo sidoo kale iyada oo loo marayo xiriirka ay u leedahay phospholipid cardiolipin ee mitochondria-gaar ah iyada oo loo marayo qaybta B-insert ee gaarka ah ee Drp1 [2]. Drp1 wuxuu caadi ahaan u jiraa sidii homotetramer-ka cytoplasm-ka, iyo isu imaatinka nidaamka sare ee goobaha fiska mitochondrial waxaa dhexdhexaadiya qaybta dhexe ee Drp1 [3].

Marka la eego xiriirka tooska ah ee u dhexeeya shaqada mitochondrial iyo dariiqa KEAP1-Nrf2-ARE, waxaan baarnay saameynta Nrf2 firfircoonida qaab dhismeedka mitochondrial iyo shaqada. Waxaan halkan ku muujineynaa in SFN ay keento hyperfusion mitochondrial taas oo, lama filaan ah, ka madax bannaan Nrf2 iyo KEAP1 labadaba. Saamayntan SFN waa iyada oo la joojinayo shaqada Drp1. Waxaan sii muujineynaa in SFN ay bixiso iska caabin ah apoptosis kaas oo ah Nrf2-madax-bannaan oo ku dayanaya in lagu arkay unugyo ka dhammaaday Drp1. Xogtaasi waxay si wadajir ah u tilmaamaysaa in marka lagu daro xasilinta iyo hawlgelinta Nrf2, SFN ay wax ka beddesho dhaqdhaqaaqa mitochondrial waxayna ilaalisaa fayaqabka iyo badbaadada gacanta.

Natiijooyinka

Sulforaphane waxay keentaa Nrf2/KEAP1-fudud ka madax-banaan ee Mitochondria

Inta lagu guda jiro daraasadda saamaynta Nrf2 firfircoonida ee dhaqdhaqaaqa shabakada mitochondrial, waxaan ogaanay in daaweynta aan dhiman karin, unugyada maqaarka maqaarka ee bini'aadamka ee epithelial (RPE-1) oo leh sulforaphane (SFN), firfircooni awood leh ee Nrf2 signaling, waxay keentay fiyuus adag oo ah shabakada mitochondrial marka la barbar dhigo unugyada kantaroolka lagu daaweeyay baabuurka (Jaantus. 1A iyo B). Qaab-dhismeedka mitochondria ee unugyadan ayaa si aad ah ugu ekaa kan mitochondria ee unugyada ay baabi'isay siRNA ee endogenous Drp1, oo ah qodobka ugu muhiimsan ee mitochondrial fission factor (Jaantus. 1A). Natiijadani waxay kicisay fikradda xiisaha leh ee mitochondrial fission iyo heerka fiyuuska ay si toos ah uga jawaabto heerarka Nrf2 ee unugyada. Si kastaba ha ahaatee, kicinta unugyada kale ee Nrf2 stabilizers iyo firfircoonayaasha sida proteasome inhibitor MG132, pro-oxidant tBHQ, ama garaacista Nrf2 inhibitor KEAP1 ma keenin mitochondrial fusion (Jaantus. 1A iyo B). Dejinta Nrf2 ee wax-is-daba-marintan ayaa lagu xaqiijiyay xannibaadda galbeedka ee Nrf2 endogenous (Jaantus. 1C). Intaa waxaa dheer, muujinta Nrf2 ayaa loo qaybin karaa isku-dhafka mitochondrial-ka ee SFN, sida garaacista Nrf2 endogenous ee siRNA ay ku guuldareysatay inay ka hortagto phenotype (Jaantus. 1DF). Sababtoo ah SFN waxay kicisaa dariiqa KEAP1-Nrf2-ARE iyadoo si wadajir ah wax uga beddelaysa hadhaaga cysteine ​​ee KEAP1 [21], waxaan hoos u dhignay KEAP1 si aan wax uga qabanno haddii SFN-ku-soo-baxa mitochondrial hyperfusion lagu kiciyo iyada oo loo marayo KEAP1-ku-tiirsan, laakiin Nrf2 dariiqo madaxbannaan. Si kastaba ha ahaatee, baabi'inta KEAP1 waxay sidoo kale ku guuldareysatay inay baabi'iso SFN-ku-takoorka mitochondrial (Jaantus. 1G�I). Dhab ahaantii, SFN waxay beddeshay qaab-dhismeedka pro-fission morphology ee ay keentay dhimista KEAP1 (Jaantus. 1G, panel b iyo panel d). Natiijooyinkani waxay muujinayaan in daawaynta SFN ay keento fiyuuska mitochondrial ee ka madax banaan dariiqa canonical KEAP1-Nrf2-ARE waxayna noo horseeday inaan su'aalo waydiino bal in SFN ay si toos ah u saamayso qaybaha mitochondrial fission ama mashiinnada fiyuuska.

Sulforaphane waxay wax u dhimaysaa Ururka Mitochondrial ee Drp1

Iyada oo ku saleysan helitaanka in daawaynta SFN ay keento hyperfusion mitochondrial, waxaan u sababeynay in phenotypeni uu yahay natiijada dhaqdhaqaaqa fiyuuska xad-dhaafka ah ama joojinta dhaqdhaqaaqa fiyuuska. Si loo takooro labadan fursadood, waxaan is barbar dhignay qaab-dhismeedka peroxisomes ee joogitaanka iyo maqnaanshaha SFN. Peroxisomes waxay la mid yihiin mitochondria sababtoo ah waxay yihiin xubno firfircoon qaabka iyo dhererka kuwaas oo si joogto ah u socda [44]. Peroxisomes waxay ka kooban yihiin Fis1 iyo Mff labadaba xuubka sare ee xuubka sare iyo, natiijadu, waa bartilmaameedyada Drp1-dhexdhexaadinta fission [22], [23]. Si kastaba ha ahaatee, peroxisomes ma isticmaalaan mishiinada isku dhafka ah ee shabakada mitochondrial oo sidaas awgeed, ma galaan fiyuuska [39]. Taa beddelkeeda, fiisigga peroxisomal waxaa ka soo horjeeda dhererka peroxisomes ee jira iyada oo loo marayo de novo ku darida xuubka iyo borotiinka [44]. Sababtoo ah peroxisomes waxay ka maqan yihiin Mfn1/2 iyo OPA1, waxaanu ku sababnay in haddii SFN ay kiciso mishiinnada fiyuuska halkii ay ka joojin lahayd mishiinka fissionka, dhererka peroxisome-ka ma saameyn doono. Unugyada gaadhiga lagu daweeyay, peroxisomes waxa loo ilaaliyaa sida gaaban, wareegsan, xubnaha punctiform (Jaantus. 2, panels b iyo d). Si kastaba ha ahaatee, daaweynta SFN waxay kordhisay dhererka peroxisome by ~ 2-laab marka la barbardhigo unugyada kantaroolka (Jaantus. 2, panels f iyo h). Intaa waxaa dheer, qaar badan oo ka mid ah peroxisomes ayaa lagu dhejiyay meel u dhow xarunta, taas oo muujinaysa cilad maqsin iman karta (Jaantus. 2, panel h, fallaadho). Sidoo kale, peroxisomes ee unugyada lagu wareejiyay Drp1 siRNA ayaa si aan caadi ahayn u dheeraa (Jaantus. 2, panels j iyo l), iyagoo xaqiijinaya in Drp1 looga baahan yahay peroxisomal fission oo soo jeedinaya in SFN-daawaynta ay keento mitochondrial iyo peroxisomal phenotypes iyada oo la carqaladaynayo mishiinka fission.

Marka xigta waxaanu go'aansanay sida SFN u xaddido shaqada Drp1. Suurtagalnimada waxaa ka mid ah hoos u dhigista heerarka odhaahda, qorista/ku haysashada mitochondria, oligomerization, ama dhaqdhaqaaqa enzymatic ee GTPase. Deficid mid ka mid ah kuwan waxay keeni doontaa hoos u dhaca mitochondrial fission iyo hyperfusion. Ma aanan ogaanin isbeddelada dib loo soo saari karo ee heerarka borotiinka Drp1 ka dib daaweynta SFN (Sawirrada 1C iyo 3A), sidaas darteed waxay soo gabagabeeyeen in SFN aysan beddelin xasilloonida Drp1 ama muujinta, waafaqsan Drp1 oo leh nolol nus ah> 10 h [50] iyo daawayntayada SFN ayaa ah mid muddo gaaban ah. Marka xigta, waxaanu baarnay in SFN ay saamaysay qorista ama ku-haynta Drp1 ee mitochondria. Daraasadaha jajabku waxay muujiyeen in SFN ay keentay lumitaanka Drp1 ee jajabka mitochondrial (Jaantus. 3A, jidadka 7�8 iyo sawirka 3B). Sida hore loo soo sheegay [43], kaliya qayb yar oo Drp1 ah (~ 3%) waxay la xiriirtaa shabakada mitochondrial wakhti kasta inta lagu jiro xaaladaha xasilloonida leh inta badan enzyme-ka ku nool cytoplasm (Jaantus. 3A, laynka 5�8). ). Xogta jajabyadan ayaa la xaqiijiyay iyadoo la adeegsanayo falanqaynta wadajirka ah taas oo muujisay ~ 40% dhimista mitochondria-localized, punctate Drp1 foci ka dib daaweynta SFN (Jaantus. 3C iyo D). Si wada jir ah, xogtani waxay tilmaamaysaa in isku-dhafka mitochondrial ee ay keentay SFN uu yahay, ugu yaraan qayb ahaan, sababtoo ah xiriirka la yareeyey ee Drp1 ee mitochondria. Xogtayadu kama kala soocayso in SFN ay farageliso qoritaanka mitochondrial iyo ku haynta mitochondrial ee Drp1, ama labadaba, maadaama falanqaynta Drp1 ee endogenous aan la aqbali karin in lagu sawiro GTPase iyada oo la adeegsanayo microscopy unug nool.

Sulforaphane waxay ka ilaalisaa Staurosportine Apoptosis ka madax banaan Nrf2

Shaqadii hore waxay muujisay in fission-ka mitochondrial uu oggol yahay samaynta daldaloolada ee xuubabka mitochondrial ee bannaanka ee ay dhaliso Bax/Bak inta lagu jiro apoptosis [11]. Drp1 ayaa la muujiyay in si xushmad leh loogu shaqaaleysiiyay mitochondria inta lagu jiro apoptosis [11] iyo, taas oo la socota tan, mitochondria kala qaybsan ayaa la arkay horaantii habka [27]. Taa bedelkeeda, xakameynta fission-ka mitochondrial waxaa loo maleynayaa in ay joojiso apoptosis iyada oo xannibaysa samaynta daloolada xuubka sare ee u oggolaanaya sii-deynta cytochrome c [53]. Sidaa darteed, kicinta fiyuuska mitochondrial ayaa dib u dhigaya horumarka apoptosis ee ay keento xeryahooda ay ku jiraan staurosporine (STS) [14]. Si loo go'aamiyo in SFN ay ka ilaaliso unugyada RPE-1 apoptosis-dhexdhexaadinta STS iyo haddii ay sidaas tahay, haddii tani ay u baahan tahay Nrf2, waxaan samaynay baaritaan si aan diyaar u ahayn poly ADP ribose polymerase (PARP) jeexjeexa, substrate of caspase-3 firfircoon iyo calaamad muujinaysa apoptosis. Daawaynta unugyada RPE-1 ee leh 1 �M STS muddo 6 saacadood ah waxa ay kaliftay kala-bax aad u yar oo PARP ah haddana tan waxa ka hortagay daawaynta SFN (tusaale, Jaantus. 4A, laynka 3 iyo 4). Si loo kordhiyo adkaanta qiimayntan, waxaanu sii dareensiinay unugyada apoptosis-ku-dhacey STS annagoo ka sii daaweynayna siRNA oo lagu beegsanayo qodobka ka hortagga apoptotic, Bcl-XL. Daawaynta ka hor waxay hoos u dhigtay muujinta Bcl-XL oo si muuqata kor loogu qaaday kala-goynta PARP taasoo ah hawl wakhti soo shaac baxday STS Muhiimad ahaan, 4 h ee daawaynta hore ee SFN la dhimay PARP kala-goynta unugyada soo gaadhay STS (Jaantus. 2C, laynka 4 iyo 10 iyo haadka 2 vs 4). Sidoo kale, unugyadii ay si adag u dhammaysteen Nrf3 ee CRISPR/Cas4 ayaa si la mid ah looga ilaaliyo sunta STS ee daawaynta hore ee SFN (Jaantus. 5C, lane 6 vs 2 iyo laynka 9 vs 4 iyo Fig. 11D). Ilaalintan waxaa lagu arkay iyadoo la isticmaalayo labadaba PARP kala-goynta (Jaantus. 12C iyo D) iyo qaab-dhismeedka unugyada (Jaantus. 13E) sida akhrinta. Waxtarka Nrf14 dhimista ee CRISPR/Cas4 ayaa lagu xaqiijiyay xannibaadda galbeedka (Jaantus. 4C, Nrf4 blot). Sida la saadaaliyay, unugyada difaaca jirka ee Drp2, kaas oo sidoo kale keena phenotype hyperfusion (Jaantus. 9A), ayaa sidoo kale xannibay dillaaca PARP ee jawaabta STS marka la barbardhigo unugyada kantaroolka ee lagu dhejiyay SFN (Sawir 4F iyo G). Wadajir ahaan, natiijooyinkani waxay la socdaan SFN oo siinaya ka-hortagga apoptosis iyada oo loo marayo awooddeeda lagu xakameynayo shaqada Drp2, oo ka madaxbannaan xasilinta iyo hawlgelinta Nrf1.

Dood

Waxaan ogaanay in SFN ay wax ka beddesho dhaqdhaqaaqa fiyuuska mitochondrial ee ka madax bannaan saameyntiisa dariiqa KEAP1-Nrf2-ARE. Tani waa mid xiiso leh sababtoo ah isku xirka la filayo ee u dhexeeya cillad la'aanta mitochondrial iyo wax soo saarka ROS iyo baahida loo qabo in la xoqo mitochondria-ka-soo-baxa xagjirnimada bilaashka ah iyada oo loo marayo hawlgelinta Nrf2. Saamayntan dheeraadka ah ee shaqaynaysa ee SFN waa muhiimad macquul ah marka la eego in ka badan 30 tijaabo caafimaad oo hadda socda baaritaanka SFN si loogu daaweeyo cudurro kala duwan oo ay ku jiraan kansarka qanjirka 'prostate', cudurada sambabada xannibaadda, iyo cudurka sickle cell [7], [10], 47].

Sababtoo ah SFN waa isothiocyanate [56] waxayna kicisaa calaamadaha Nrf2 iyada oo si toos ah u kicinaysa KEAP1 cysteinees muhiim ah si loo xakameeyo Nrf2 hoos u dhaca [21], waxay raacdaa in SFN ay sameyso saameynteeda faleebo iyada oo hagaajinaysa waxqabadka fission ama faleebo iyada oo loo marayo hagaajinta cysteine. . Xogtayadu waxay si xoog leh u taageertaa Drp1 inay si xun u maamusho SFN in kasta oo in GTPase uu yahay bartilmaameed toos ah oo la taaban karo ayaa weli ah mid la caddeeyey. Inkasta oo farqiga aqoontan, shaqada Drp1 ay si cad u dhibayso SFN maaddaama labada mitochondria iyo peroxisomes ay noqdaan kuwo aad u sarreeya oo ka jawaabaya daaweynta SFN iyo xubnahani waxay la wadaagaan Drp1 dhacdooyinkooda maqaarka [38]. Intaa waxaa dheer, SFN waxay hoos u dhigtaa qaddarka Drp1 ee meeleeya oo ku urura mitochondria (Sawir. 3). Sababtoo ah tijaabooyinkeena waxaa lagu sameeyay dhammaan borotiinada endogenous, ogaanshahayaga Drp1 ee goobaha mitochondrial fission waxay ku hoos jiraan xaalado joogto ah, sidaas awgeed, ma kala saari karno shaqaaleysiinta iyo cilad sii haynta enzyme ay sababtay SFN. Dheeraad ah, ma baabi'in karno suurtagalnimada in SFN acylates a reseptor at mitochondria (Fis1 ama Mff) si loo joojiyo qoritaanka Drp1 weli, waxaan ka shakisanahay in Drp1 si toos ah wax laga beddelay. Drp1 waxay leedahay sagaal cysteinees, siddeed ka mid ah waxay ku nool yihiin gudaha Domain-ka Dhexe ee looga baahan yahay oligomerization [3], mid ka mid ahna wuxuu degan yahay GTPase Effector Domain (GED) ee C-terminus ee Drp1. Dhaqdhaqaaqa tooska ah ee mid kasta oo ka mid ah cysteins-yadan waxay sababi kartaa cillad hawleed oo ku jirta Drp1 sidaas darteedna waxay hoosta ka xariiqaysaa saameynta SFN ee dhaqdhaqaaqa mitochondrial. Waxaa xusid mudan, shaqada hore waxay soo jeedinaysaa in cilladaha oligomerization iyo dhaqdhaqaaqa kicinta ay baabi'in karaan sii-haynta Drp1 ee mitochondria [52]. Cys644 ee GED domain waa bartilmaameed gaar ah oo soo jiidasho leh oo ku salaysan shaqo hore oo muujinaysa in isbeddelka isbeddellada cysteine ​​phenocopies ee wax u dhimaya Drp1 GTPase dhaqdhaqaaqa [4] iyo in cysteine-kan gaarka ah uu wax ka beddelayo electrophiles thiol-reactive [9]. Xallinta su'aashan cajiibka ah waxay u baahan doontaa ansaxinta spectrometric mass. Soo koobid, waxaanu aqoonsanay sheeko cusub, shaqada cytoprotective ee xarunta SFN ee kiliinikada ku xidhan. Marka lagu daro kicinta mawduuca qoraalka anti-oxidant ee Nrf2, SFN waxay kor u qaadaa mitochondrial iyo peroxisomal fusion, saameyntani waxay ka madax banaan tahay Nrf2. Habka hoosta ka xariiqaya dhacdadani waxay ku lug leedahay hoos u dhigista shaqada GTPase Drp1, dhexdhexaadiyaha aasaasiga ah ee mitochondrial iyo peroxisomal fission. Cawaaqibta ugu weyn ee SFN-dhexdhexaadinta mitochondrial fusion waa in unugyadu noqdaan kuwo u adkaysta saamaynta sunta ah ee staurosporine inducer apoptosis. Ficilkan cytoprotective ee dheeraadka ah ee SFN wuxuu noqon karaa mid ka mid ah faa'iidooyin caafimaad oo gaar ah oo ku saabsan cudurro badan oo neurodegenerative kuwaas oo da'doodu tahay khatarta ugu weyn (tusaale ahaan, Cudurka Parkinson, Cudurka Alzheimers, Cudurka Macular Degeneration) maaddaama cudurradan ay la xiriireen apoptosis oo la yareeyey. heerarka iyo/ama habacsanaanta Nrf2 [35], [36], [48].

Qalabka iyo Dariiqooyinka

Apoptosis Asays

Unugyada waa la abuurey waxaana lagu kala wareejiyey siRNA sida hoos ku cad. Unugyada waxaa horay loogu daaweeyay 50 ?M sulforaphane 2 saac si ay u keenaan fiyuuska mitochondrial ka dibna waxaa lagu daaweeyay 1?M staurosporine si loo keeno apoptosis. Waqtiga goosashada, warbaahinta waxaa lagu soo ururiyay tuubooyin gaar ah waxaana lagu sammeeyay centrifugation xawaare sare leh unugyada apoptotic pellet. Pellet-ka unugga waxa lagu daray unugyo ku dheggan waxaana lagu milmay 2 jeer-koob-saar Laemmli ah. Muunado ayaa lagu sameeyay ka hortagga PARP-da-dabaynta.

Jiilka Dhismaha CRISPR/Cas9

Si loo abuuro LentiCRISPR/eCas9 1.1, LentiCRISPR v2 (ku dar #52961) ayaa markii hore lagu gooyay Age1 iyo BamH1. Marka xigta, SpCas9 ee eSpCas9 1.1 (addgene #71814) ayaa PCR lagu xoojiyey Age1 iyo BamH1 overhangs iyadoo la adeegsanayo aasaasayaasha soo socda. taxanaha sgRNA waxaa lagu go'aamiyay iyadoo la isticmaalayo Benchling.com. Halbeegyada waxaa loo dejiyay in lagu beegsado isku xigxiga kood-samaynta oo leh bartilmaameedka ugu sarreeya iyo kuwa ugu hooseeya ee bartilmaameedka ah. The isku xigxigta soo socda (xigxiga lala beegsaday hoosta ka xariiqay, HS sgNFE2L2 # CACCGCGACGGAAAGAGTATGAGC 1 dareen, AAACGCTCATACTCTTTCCGTCGC antisense, HS sgNFE2L2 # 2 CACCGGTTTCTGACTGGATGTGCT dareen, AAACAGCACATCCAGTCAGAAACC antisense, HS sgNFE2L2 # 3 dareen CACCGGAGTAGTTGGCAGATCCAC, AAACGTGGATCTGCCAACTACTCC antisense) ayaa annealed iyo ligated galay BsmB1 jaray LentiCRISPR / eCas9 1.1. Unugyada RPE-1 ee cudurka lentivir ayaa lagu xushay puromycin waxaana lagu ilaaliyay sidii dad la ururiyey. Garaacida waxaa lagu xaqiijiyay difaaca jirka iyo xinjirowga galbeedka.

Dhaqanka Unugyada iyo Is-beddelka

Unugyada epithelial pigment retinal ee bini'aadamka oo lagu beddelay telomerase (RPE-1) (ATCC) ayaa lagu dhaqan geliyay Dulbecco's Modified Eagle Medium (DMEM) oo ka kooban 1 g/L gulukoos lagu kabay penicillin, streptomycin, 1X amino acid cocktail aan muhiim ahayn (Technology Life), iyo 10% uurjiifka Serum Bovine (Technology Life). SiRNA-is-beddelka, 30,000–35,000 unug/mL ayaa la beeray habeen qura. Unugyadu waxay heleen 10 nM siRNA oo lagu qasi jiray DMEM-free serum oo lagu daray 0.3% reagent wareejinta interferin (PolyPlus). Dareenka apoptosis, unugyadu waxay heleen 1 nM Bcl-XL siRNA. Unugyada ayaa la goostay 2-3 maalmood ka dib markii la beddelay.

Kiimikooyinka, unugyada difaaca jirka, iyo siRNA Oligos

Unugyada ka-hortagga ?-tubulin (Calaamadaha unugga), ?-tubulin (Sigma), Drp1 (BD Biosciences), KEAP1 (Proteintech), Lamin B1 (Abcam), PARP (Calaamadaha unugyada), PMP70 (Abcam), iyo Tom20 (BD Biosciences). ) waxa loo isticmaalay 1:1000 dilutions loogu talagalay dhufashada galbeedka iyo immunofluorescence. Guriga dhexdiisa, anti-Nrf2 antibody bakayle ayaa loo isticmaalay 1:2000 ee galbeedka [34], [59]. Sulforaphane (Sigma) iyo staurosporine (Tocris) ayaa loo isticmaalay 50 ?M iyo 1?M siday u kala horreeyaan. siRNAs ka dhanka ah Drp1 (Dharmacon), Nrf2 (Dharmacon), KEAP1 (Calaamadaha Unugyada), iyo Bcl-XL (Calaamaynta Unugyada) ayaa loo adeegsaday 10 nM ilaa si kale loo xuso.

Immunofluorescence iyo calaamadaynta Vivo

Unugyada lagu beeray daboolka muraayadaha 18 mm waxaa lagu daaweeyay baabuur ama daroogo, lagu hagaajiyay 3.7% formaldehyde ka dibna la dalacsiiyay 0.2% Triton X-100/PBS baraf 10 min. Unugyada difaaca ee aasaasiga ah ayaa lagu darey 3% serum albumin (BSA) ee PBS habeennimadii 4 ℃. Ka dib dhaqidda PBS, unugyadu waxay ku jireen 1 h noocyada ku habboon, Alexa488- ama Alexa546-, unugyada difaaca sare ee isku dhafan (la badhxay 1: 1000) iyo 0.1?g/mL DAPI (Sigma) ee 3% BSA/PBS. Mitochondria waxaa lagu sawiray mid ka mid ah anti-Tom20 immunofluorescence ama iyada oo la abuurayo unugyada 200 nM MitoTracker Red CMXRos (Molecular Probes, Inc.) ee DMEM-free DMEM ee 30 min at 37 �C kahor hagaajinta.

Faaqidaadda mikroskoobiyaha iyo sawirka

Saambalada Immunofluorescence ayaa lagu arkay LSM710 Confocal microscope (Carl Zeiss). Micrographs ayaa la qabtay iyadoo la adeegsanayo 63X ama 100X ujeeddooyinka immersion saliidda iyo sawirada la hagaajiyay lana xoojiyey iyadoo la isticmaalayo Adobe Photoshop CS6. Falanqaynta isku-dejinta waxa la sameeyay iyada oo la adeegsanayo Carl Zeiss LSM710 sifada wada-dejinta oo leh marino gacanta loo dejiyay iyada oo indhaha laga qariyay aqoonsiga shaybaarada. Baararka miisaanka oo dhan, ilaa si kale loo tilmaamo, waa 10 �m. Mitochondrial morphology waxaa lagu qiimeeyay dhibco indho la'aan ah. Haddii mitochondria unug lagu hayo tiro badan, wareegsan, puncta takoorid, unugga waxa loo dhaliyay sidii �fission�. Haddii mitochondria shakhsi ahaaneed aan la kala saari karin oo dhammaan shabakada mitochondrial ay u muuqatay mid joogto ah, unugga waxaa loo dhaliyay sida �fusion�. Dhammaan unugyada kale, oo ay ku jiraan kuwa leh mitochondria, ayaa loo dhaliyay si dhexdhexaad ah.

Qaybaha unugyada hoose

Unugyada RPE-1 ayaa la koray si ay isugu yimaadaan. Ka dib markii la dhaqay PBS, unugyadu waxaa lagu sarifay centrifugation at 600�g 10 min waxaana dib loo hakiyay 600 ?L karantiilka (210 mM Mannitol, 70 mM Sucrose, 5 mM MOPS, 1 mM EDTA pH 7.4+1 mM PMSF). Hakinta ayaa 30 jeer lagu dhuftay isku-dhafka Dounce. Qayb ka mid ah homogenate-ka ayaa loo xafiday sidii unug dhan lysate. Kuwa sare waxa lagu sarifay centrifugation at 800�g 10 daqiiqo si ay u nadiifiyaan nukleiyada hadhay iyo unugyo aan la xidhin. Dabeecaddan sare waxa lagu sarifay centrifugation 1500�g 10 daqiiqo ilaa pellet mitochondria. Ka sarreeya waxa loo xafiday sida jajabka cytosolic. Pellet-ka ayaa si tartiib ah loogu maydhay PBS waxaana dib loo hakiyay iyada oo go'doon ah. Xaddiga borotiinka ee jajab kasta waxa lagu qiyaasay bicinchoninic acid (BCA) qiimaynta iyo cadadka borotiinka ee u dhigma ayaa lagu xalliyay SDS-PAGE.

Western Blotting

Unugyada waxaa lagu dhaqay PBS waxaana lagu milmay 2 jeer oo la isku koobay Laemmli solubilizing buffer (100 mM Tris [pH 6.8], 2% SDS, 0.008% bromophenol blue, 2% 2-mercaptoethanol, 26.3% glycerol, iyo 0.001%). Lysates ayaa la karkariyey 5 daqiiqo ka hor inta aan la saarin sodium dodecyl sulfate (SDS) jellaha polyacrylamide. Barootiinnada waxaa loo wareejiyay xuubka nitrocellulose xuubkana waa la xiray 1 saac 5% Caano/TBST. Unugyada difaaca ee asaasiga ah waxaa lagu milmay 5% Caano/TBST waxaana lagu tallaalay xuubka habeenkii 4 �C. Horseradish peroxidase (HRP) - unugyada difaaca jirka labaad ee isku dhafan ayaa lagu qasi jiray 5% Caano/TBST. Burooyinka waxaa lagu farsameeyay chemiluminescence la xoojiyay iyo qiyaasaha densitometric ayaa la sameeyay iyadoo la isticmaalayo software ImageJ.

Sulforaphane waa kiimiko ka soo ururinta isothiocyanate ee walxaha organosulfur ee laga helo khudaarta cruciferous, oo ay ku jiraan brokoli, kaabajka, cauliflower, kale, iyo collars, iyo kuwo kale. Sulforaphane waxa la soo saaraa marka ensaymka myrosinase uu u beddelo glucoraphanin, glucosinolate, sulforaphane, oo sidoo kale loo yaqaan sulforaphane-glucosinolate. sprouts Broccoli iyo tayo sare leh ayaa leh heerka ugu sarreeya ee glucoraphanin ama horudhaca sulforaphane. Daraasado cilmi baaris ah ayaa muujiyay in sulforaphane ay kor u qaaddo awoodaha antioxidant ee jirka bini'aadamka si looga hortago arrimo caafimaad oo kala duwan. Dr. Alex Jimenez DC, CCST Insight

Sulforaphane iyo Saameyntiisa Kansarka, Dhimashada, Gabowga, Maskaxda iyo Dhaqanka, Cudurrada Wadnaha & in ka badan

Isothiocyanates waa qaar ka mid ah xeryahooda dhirta ee ugu muhiimsan ee aad ka heli karto cuntadaada. Fiidiyowgaan waxaan u sameynayaa kiiskii ugu badnaa ee abid la sameeyo. Fiiro gaar ah oo gaaban? U gudub mawduuca aad jeceshahay adiga oo gujinaya mid ka mid ah dhibcaha wakhtiga hoose. Jadwalka wakhtiga oo buuxa hoos

Qaybaha muhiimka ah:

• 00:01:14 - Kansarka iyo dhimashada
• 00:19:04 - gabowga
• 00:26:30 - Maskaxda iyo dhaqanka
• 00:38:06 - Dib u soo koobid kama dambays ah
• 00:40:27 - Qiyaasta

Waqtiga buuxa:

• 00:00:34 - Horudhaca sulforaphane, diiradda weyn ee fiidiyowga.
• 00:01:14 - Cunista khudaarta caleenta leh iyo hoos u dhigista dhammaan dhimashada.
• 00:02:12 - Khatarta kansarka qanjirka 'prostate'.
• 00:02:23 - Khatarta kansarka kaadiheysta.
• 00:02:34 - Kansarka sambabada ee sigaarka cabba.
• 00:02:48 - Khatarta kansarka naasaha.
• 00:03:13 - mala awaal: ka waran haddii aad hore u qabtid kansar? (dhexdhexaad ah)
• 00: 03: 35 - Habka macquulka ah ee wadista kansarka iyo xogta xiriirka dhimashada.
• 00:04:38 - Sulforaphane iyo kansarka.
• 00: 05: 32 - Caddaynta xayawaanka oo muujinaysa saamaynta xooggan ee brokoli ka soo baxa burooyinka ee horumarinta burooyinka kaadiheysta ee jiirka.
• 00:06:06 - Saamaynta kabista tooska ah ee sulforaphane ee bukaanka kansarka qanjirka 'prostate'.
• 00: 07: 09 - Bioaccumulation of metabolites isothiocyanate ee nudaha naaska dhabta ah.
• 00:08:32 - Joojinta unugyada asliga ah ee kansarka naasaha.
• 00:08:53 - Casharka taariikhda: brassicas waxaa loo aasaasay inay leeyihiin sifooyin caafimaad xitaa Rome hore.
• 00:09:16 - Awoodda Sulforaphane si kor loogu qaado soosaarka kansarka (benzene, acrolein).
• 00: 09: 51 - NRF2 sida beddelka hiddaha iyada oo loo marayo walxaha jawaabta antioxidant.
• 00: 10: 10 - Sida firfircoonida NRF2 ay kor ugu qaaddo qashinka kansarka iyada oo loo marayo glutathione-S-conjugates.
• 00: 10: 34 - sprouts Brussels waxay kordhiyaan glutathione-S-transferase waxayna yareeyaan dhaawaca DNA.
• 00:11:20 - Cabitaanka sprout broccoli wuxuu kordhiyaa soosaarka benzene 61%.
• 00: 13: 31 - Broccoli sprout homogenate waxay kordhisaa enzymes antioxidant ee marinka hawada sare.
• 00: 15: 45 - Cunista khudaarta cruciferous iyo dhimashada cudurrada wadnaha.
• 00: 16: 55 - Budada sprout broccoli waxay hagaajinaysaa dufanka dhiigga iyo guud ahaan khatarta cudurrada wadnaha ee nooca 2 ee sonkorowga.
• 00:19:04 - Bilawga qaybta gabowga.
• 00: 19: 21 - Sulforaphane-cuntooyinka qani ku ah waxay kor u qaadaan cimriga kuwa lamid ah 15 ilaa 30% (xaalad gaar ah).
• 00: 20: 34 - Muhiimadda caabuqa hooseeya ee muddada dheer.
• 00: 22: 05 - Khudaarta cruciferous iyo budada broccoli waxay u muuqdaan inay yareeyaan calaamado kala duwan oo barar ah oo bini'aadamka ah.
• 00:23:40 - Dib u habeynta fiidiyowga dhexe: kansarka, qaybaha gabowga
• 00:24:14 - Daraasadaha jiirka ayaa soo jeedinaya in sulforaphane laga yaabo inay wanaajiso shaqada difaaca la qabsiga ee da'da.
• 00:25:18 - Sulforaphane waxay hagaajisay koritaanka timaha ee qaabka jiirka ee bidaarta. Sawirka 00:26:10.
• 00:26:30 - Bilawga maskaxda iyo qaybta habdhaqanka.
• 00:27:18 - Saamaynta brokoli ee ka soo baxa cudurka autism.
• 00:27:48 - Saamaynta glucoraphanin ee shisoofrani.
• 00: 28: 17 - Bilawga wadahadalka niyad-jabka (farsamo macquul ah iyo daraasado).
• 00: 31: 21 - Daraasada jiirka iyadoo la adeegsanayo 10 nooc oo kala duwan oo niyad-jabka ah ayaa muujinaya sulforaphane si la mid ah waxtarka sida fluoxetine (prozac).
• 00: 32: 00 - Daraasadu waxay muujineysaa in si toos ah loo nuugo glucoraphanin ee jiirarka ay si la mid ah waxtar ugu leedahay ka hortagga niyad-jabka ee ka timaadda qaabka cadaadiska bulshada.
• 00: 33: 01 - Bilawga qaybta neurodegeneration.
• 00:33:30 - Sulforaphane iyo cudurka Alzheimers.
• 00:33:44 - Sulforaphane iyo cudurka Parkinson.
• 00:33:51 - Sulforaphane iyo cudurka Hungtington.
• 00: 34: 13 - Sulforaphane waxay kordhisaa borotiinnada shoogga kulaylka.
• 00:34:43 - Bilawga qaybta dhaawaca maskaxda ee dhaawaca ah.
• 00: 35: 01 - Sulforaphane ayaa la isku duraa isla markiiba ka dib markii TBI ay wanaajiso xusuusta (daraasadda jiirka).
• 00: 35: 55 - Sulforaphane iyo caagagga neuronal.
• 00:36:32 - Sulforaphane waxay wanaajisaa barashada qaabka nooca II ee sonkorowga ee jiirarka.
• 00:37:19 - Sulforaphane iyo duchenne dystrophy muruqa.
• 00: 37: 44 - Joojinta Myostatin ee unugyada satalaytka muruqa (in vitro).
• 00: 38: 06 - Dib u soo celinta fiidiyowga dambe: dhimashada iyo kansarka, dhaawaca DNA, cadaadiska oksaydhka iyo bararka, dheecaanka benzene, cudurada wadnaha, nooca II ee sonkorowga, saameynta maskaxda (niyad-jabka, autism, schizophrenia, neurodegeneration), waddada NRF2.
• 00:40:27 - Fikradaha lagu ogaanayo qiyaasta brokoli sprouts ama sulforaphane.
• 00:41:01 - Sheekooyinka ku saabsan biqilka guriga.
• 00:43:14 - On heerkulka karinta iyo hawlaha sulforaphane.
• 00:43:45 - Beddelka bakteeriyada Gut ee sulforaphane ee glucoraphanin.
• 00: 44: 24 - Kaabisyadu waxay si fiican u shaqeeyaan marka lagu daro myrosinase firfircoon ee khudaarta.
• 00:44:56 - Farsamooyinka karinta iyo khudaarta cruciferous.
• 00:46:06 - Isothiocyanates sida goitrogens.

Mahadnaq

Sciencedirect.com/science/article/pii/S2213231716302750

Sidee loo soo saaraa Sulforaphane?

Kululaynta waxay hoos u dhigtaa dhaqdhaqaaqa borotiinka Epithiospecifier waxayna kordhisaa Samaynta Sulforaphane ee Brokoli

aan la taaban karin

Sulforaphane, isothiocyanate ka brokoli, waa mid ka mid ah anticarcinogen-ka ugu awoodda badan cuntada. Xaruntani kuma jirto khudradda aan nadiifka ahayn, halkii ay ka samaysan tahay horudhackeeda glucosinolate, glucoraphanin, oo ay samaysay ficilka myrosinase, enzyme thioglucosidase, marka nudaha broccoli la jajabiyo ama la ruugo. Si kastaba ha ahaatee, tiro daraasado ah ayaa muujiyay in wax-soo-saarka sulforaphane ee glucoraphanin uu hooseeyo, iyo in analog nitrile aan bioactive ahayn, sulforaphane nitrile, waa sheyga asaasiga ah ee hydrolysis marka unugyada dhirta lagu burburiyo heerkulka qolka. Caddaynta dhawayd waxay soo jeedinaysaa in Carabidopsis, samaynta nitrile ee glucosinolates ay maamusho borotiinka xasaasiga ah ee kulaylka, borotiinka epithiospecifier (ESP), cofactor non-catalytic of myrosinase. Ujeeddooyinkayagu waxay ahaayeen inaan baaro saamaynta kulaylka ubaxa broccoli iyo sprouts on sulforaphane iyo sulforaphane nitrile formation, si loo go'aamiyo haddii brokoli ay ka kooban tahay waxqabadka ESP, ka dibna si loo hagaajiyo isbeddelada ku-tiirsanaanta ku-tiirsanaanta ee hawlaha ESP, content sulforaphane iyo bioactivity, sida lagu qiyaaso soo-gelinta wajiga II detoxification enzyme quinone reductase (QR) ee dhaqanka unugyada. Kuleylinta ubaxa broccoli cusub ama brokoli waxay soo baxdaa ilaa 60C ka hor isku dhafka isku mar waxay kordhisay samaynta sulforaphane waxayna hoos u dhigtay samaynta nitrile sulforaphane. Lumitaanka muhiimka ah ee dhaqdhaqaaqa ESP ayaa barbar socday hoos u dhaca samaynta nitrile sulforaphane. Kuleylinta ilaa 70ºC iyo wixii ka sareeya waxay hoos u dhigtay samaynta labada badeecadood ee ubaxa brokoli, laakiin kuma jiraan sprouts broccoli. Soo saarista QR ee jiirka hepatoma Hepa lclc7 unugyo isbarbar socda ayaa kordhay samaynta sulforaphane.

Kuleylinta brokoli ka hor ubaxyada iyo sprouts ilaa 60ºC waxay si weyn u kordhisay samaynta myrosinase-catalyzed ee sulforaphane (SF) ee laga soosaaray unugyada khudradda ka dib markii la burburiyo. Tani waxay la xidhiidhay hoos u dhaca samaynta sulforaphane nitrile (SF Nitrile) iyo borotiinka epithiospecifier (ESP).

Keywords: Broccoli, Brassica oleracea, Cruciferae, Kansarka, Anticarcinogen, Sulforaphane, Sulforaphane nitrile, borotiinka Epithiospecifier, Quinone reductase

Gabagabadii, sulforaphane waa kiimiko phytochemical ah oo laga helo brokoli, iyo khudaarta kale ee cruciferous. Qaddarka oksaydhiyeyaasha aan la koontaroolin ee ay sababaan arrimaha gudaha iyo dibaddaba waxay sababi karaan diiqad oksijiyeedka jirka bini'aadamka taasoo ugu dambeyntii horseedi karta arrimo caafimaad oo kala duwan. Sulforaphane waxay dhaqaajin kartaa wax soo saarka Nrf2, oo ah arrin qoraal ah oo gacan ka geysata habeynta hababka difaaca jirka ee xakameynaya jawaabta unugga ee oksaydhiyeyaasha. Baaxadda macluumaadkayadu waxay ku kooban tahay xanuunka loo yaqaan 'chiropractic' iyo arrimaha caafimaadka laf dhabarta. Si aad ugala hadasho mawduuca, fadlan xor u noqo inaad waydiiso Dr. Jimenez ama nagala soo xidhiidh at�915-850-0900 .

Waxaa soo saaray Dr. Alex Jimenez

Waxaa laga tixraacay: Sciencedirect.com

Mawduuc Dheeraad ah: � Xanuun Dhabar Ba'an

Xanuunka dhabarka�waa mid ka mid ah sababaha ugu badan ee naafada iyo maalmaha shaqada ka baaqda ee adduunka oo dhan. Xanuunka dhabarka ayaa loo aaneynayaa sababta labaad ee ugu badan ee booqashooyinka xafiiska dhakhtarka, oo ay ka badan yihiin kaliya caabuqyada neef-mareenka sare. Qiyaastii 80 boqolkiiba dadku waxay la kulmi doonaan xanuunka dhabarka ugu yaraan hal mar noloshooda oo dhan. Laf-dhabarta waa qaab dhismeed kakan oo ka kooban lafo, kala-goysyo, seedaha, iyo murqaha, iyo unugyo kale oo jilicsan. Taas awgeed, dhaawacyada iyo/ama xaaladaha sii xumeeyay, sida�maqaarka herniated, ugu dambeyntii waxay keeni kartaa calaamadaha xanuunka dhabarka. Dhaawacyada isboortiga ama dhaawacyada shilalka baabuurta ayaa inta badan ah sababta ugu badan ee xanuunka dhabarka, si kastaba ha ahaatee, mararka qaarkood dhaqdhaqaaqa ugu fudud ayaa keeni kara natiijooyin xanuun leh. Nasiib wanaag, xulashooyinka daaweynta kale, sida daryeelka xanuunka loo yaqaan 'chiropractic care', ayaa kaa caawin kara yareynta xanuunka dhabarka iyada oo loo marayo isticmaalka isbeddelka laf-dhabarka iyo manfacyada gacanta, ugu dambeyntii hagaajinta xanuunka.

DHEERAAD AH | Mawduuca MUHIIMKA AH: Lagu taliyay El Paso, TX Chiropractor

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