Te puru metilīni hei matū ārai-whakahāoratanga, hei matū whakatairanga-whakahāoratanga hoki: he aha e rerekē ai te putanga?

Whakaarohia ka whakamātautau ngā taiwhanga e rua i te waikano puru kotahi, ā, ka pūrongo i ngā hua tauaro. I te taiwhanga tuatahi, ka pai ake te hā o ngā mitokōria roro kua wehea, ā, ka nui ake te ATP ka hangaia. I te tuarua, ka tukuna e taua takanga tonu he hauwai perōkai tino nui ake. E tika ana ngā pūrongo e rua. E whakaahua ana i te huringa kotahi, engari e tirohia ana mai i ōna pito e rua. Ka tīmata te rangirua ina whakaarohia e ngā kaipānui ko tētahi pito te kōrero katoa.

Ko te hē, ko te pātai ko tēhea tapanga e tika ana mō te rāpoi ngota. He kaikawe irahiko te puru metilīni, e whakaaturia ana i roto i te horopaki whānui ake e te mahere o ōna ūnga koiora pūtau. Ka tango te waikano kua whakahāoratia i ngā irahiko, ā, ka huri hei leucoMB kore tae. Ka tuku atu te leucoMB i aua irahiko, ā, ka puru anō. Ko tāu e kite ai ka whakawhirinaki ki te kaituku irahiko, ki te kaiwhiwhi, me te āhei o te pūnaha ki te whakawātea i te hauwai perōkai ka hangaia i te ara. Ehara te pātai whai take i te mea he matū ārai-whakahāoratanga rānei te waikano. Ko te pātai kē, he aha ngā mahi ka whakaaetia e ngā āhuatanga mō taua whakawhitinga irahiko.

Te huringa e puta ai ngā āhua e rua

I te pōuri, he poto te huringa matua. Ka whakaheke te NADH, te NADPH, ngā kaikawe rānei o te mekameka hā i te waikano. Kātahi ka whai ara whakataetae te waikano kua whakahekea. Ka taea te tuku irahiko ki te cytochrome c, ka tautoko i te rere mā tētahi ara karo i te matatini kua tūkinotia. Nā reira ka āhua hoki mai te hā me te pūmanawa kiriuhi ina āraia te matatini I, III rānei. Ka taea rānei te tuku irahiko hāngai ki te hāora, ka whakahou i te āhua puru, ka hanga hoki i te hauwai perōkai. Nā te whakahoutanga o te waikano, ka taea e tētahi rahinga iti te tukurua i tēnei huringa i ngā wā maha, me te kai haere tonu i ngā ōritenga whakaheke, me te hanga haere tonu i te perōkai.

E rua anō ngā peka ka tino whakarerekē i te matū. Ka huri te konukura herekore, te rino herekore rānei i taua perōkai ka taea te marara, hei matū whakahāora ā-rohe tino kino ake, mā ngā tauhohenga momo Fenton. Ka whakatuwhera te mārama whero i tētahi peka matū-ā-mārama motuhake: ka tuku pūngao te waikano kua whakaohohia ki te hāora, ka hanga i te hāora takitahi. Ka whakamāramatia whānuitia taua momo i roto i te whakamārama mō te matū-ā-mārama momo I me te momo II. He tikanga rerekē e toru te huringa whakaheke-whakahāora i te pōuri, te tūkinotanga ka whakanuia e ngā konganuku, me te tūkinotanga ā-mārama; kotahi noa iho tō rātou rāpoi ngota tīmatanga.

Te tūtohi āhuatanga me ngā putanga

Ko te ripanga kei raro nei te rauemi hei pupuri. Kei ia rārangi tētahi taurangi, te ahunga ka panaia e taua taurangi, me te whakamātautau hei taunaki. Ko te pai he inenga e tohu ana i te tiakitanga, i te whakapaitanga rānei. Ko te kino he nui ake te matū whakahāora, te pau o ngā matū, te tūkinotanga rānei.

Ko te tauira puta noa i ngā rārangi te aronga matua. He tuaka motuhake te whakaputanga perōkai me te tiakitanga koiora. Ka taea e tētahi maimoatanga te whai hua kino i te tuaka tuatahi, me te hua pai i te tuaka tuarua i taua wā tonu.

He aha i rerekē ai ngā whakautu mō te horopeta kotahi

Mā te kukū e whakatau te kaha kawe irahiko, ehara i te mutunga. I piki te tukunga perōkai mai i ngā mitokōria roro kia kitea ai, mai i te 50 nM whakarunga, i roto i te rangahau mō ngā mitokōria roro mau tonu. Engari me 100 uM i te pōuri kia puta ai te tūkinotanga DNA mitokōria mārama. Nō reira, he āputa tata ki te rua mano whakareatanga i waenga i te tohu tuatahi me te tūkinotanga ki te ira, engari ehara tēnei i te tawhē haumaru. He rerekē ngā putanga ka inea, ngā wāhi o roto, me ngā wā pānga, nō reira e tohu ana ngā tau i ngā tūāhua motuhake, kaua i ngā wāhi i runga i te ānau kotahi. Ka whakatakoto te matapaki urupare ki te horopeta i tēnei momo āputa i waenga i te tohu iti me te tūkinotanga nui ki tōna horopaki hormesis whānui ake.

Mā te matū taketake e whakatau te wāhi e kuhu ai ngā irahiko. Ka hoatu e ngā wahie hono ki te NADH ngā ōritenga whakaheke maha ki te waikano, mō te ara karo whaihua me te tauhohenga hāora moumou hoki. Ko te whakarāpopototanga e whakahuatia nuitia ana, arā, mā te sukināta te waikano e mahi hei ārai-whakahāora, mā te kutamāta hei whakatairanga-whakahāora, he whakatau nui rawa i runga i ngā raraunga. Ko te take, i roto hoki te rotenōne i te āhuatanga perōkai sukināta o te rangahau manawa, ā, i whakamahia he kiko me te horopeta rerekē i ērā o te rangahau roro i kite ai i te pikinga o te perōkai i raro i ia matū taketake me ia āhua hā.

Ka hurihia e te mārama te tikanga, ehara i te rahinga anake. Ko te whakatauritenga tino mārama o te huinga, ko te 20 uM i te pōuri, kāore i pā he rerekētanga kitea ki ngā wāhanga DNA mitokōria, me te 20 uM i raro i te mārama whero, i tūkinotia ai aua wāhanga katoa. Ko te tangata e whakataurite ana i tētahi whakamātautau whai mārama ki tētahi i te pōuri, e whakataurite ana i te matū-ā-mārama ki te huringa whakaheke-whakahāora.

Ka hurihia e ngā konganuku te matū whakahāora. Ki te kore he konganuku, ka hanga te huringa pōuri o te waikano i te perōkai, he rāpoi ngota ka taea te marara, ā, ka whakamahia hoki e ngā pūtau hei tohu. Ki te wātea te konukura, te rino rānei, ka tautoko te waikano kua whakahekea e te NADH i te whakahekenga konganuku. Kātahi te konganuku kua whakahekea ka whakahohe i te perōkai hei momo hydroxyl, hei momo perōkai konukura rānei, i te taha o te DNA. Koinei te huarahi i puta ai te tūkinotanga DNA kōwhiri i ngā wāhi tairongo me te tūkinotanga whānui mai i taua waikano tīmatanga kotahi i roto i te rangahau kore pūtau me te NADH me ngā katote konganuku. Mā te whakahaerenga konganuku o te wāhi o roto, ehara mā te waikano anake, e whakatau mēnā he mea nui tēnei peka.

Mā te āhua o te wahie e whakatau mēnā ka taea e te pūtau te utu. I roto i ngā pūtau endothelium i pāngia ki te 2 ki 20 uM waikano, nā te tango kūhuka i kitea ai te utu whakahāora, ā, nā te tuku kūhuka i whakakore taua utu, ahakoa i whakatere hoki te kūhuka i te whakahekenga waikano. He pai ake te huringa tere me ngā ārai whai rauemi i te huringa pōturi me ngā ārai kore rauemi. Me whakaaro he kōrero kāore anō kia oti ngā kerēme matū whakahāora e mahue ana te āhua o te kūhuka, o te NADPH rānei.

Mā te kiko e whakatau ngā taputapu koiora. Ka whakahou ngā pūtau endothelium i te NADPH mā te pākia kūhuka, ā, he puna matū ārai-whakahāoratanga kei roto i te wai pūtau. Kāore aua mea i ngā mitokōria kua wehea. Kāore hoki he whakatikatika i te DNA kua purea. He iti noa te āwhina o tētahi hua i tētahi takanga ki te matapae i ngā hua o ērā atu. Nā reira me wehe tonu ēnei pūnaha i roto i te tuhinga kua whakamaheretia mō ngā urupare motuhake o ia kiko.

Ehara te inenga hāngai i te ārai ka whai mai

He maha ngā tuhinga ka whakakotahi i ngā paparanga e rua e wehea ana e ngā whakamātautau. Ko tētahi paparanga ka pātai e hia te matū whakahāora i puta. Ko tētahi atu ka pātai i pēhea te urupare a te pūtau.

Ko ngā whakamātautau perōkai momo Amplex ngā mea e tata rawa ana ki te paparanga tuatahi. Ahakoa ēnei, ko tā rātou e pūrongo ai ko te rerenga toenga: ko te whakaputanga, ka tangohia te whakangaromanga me te tukunga ki waho. I kitea e te rangahau mitokōria roro te neke o ngā taha e rua: he nui ake te perōkai i hangaia, ā, he pōturi ake te whakawātea i tētahi rahinga perōkai i tāpirihia i te wā kotahi. Kei tua atu i te ara te whakahāoratanga kutataione, te paunga askōpāta, te kuanīni kua whakahāoratia, me ngā wharanga DNA e ārai ana i te polymerase. Ka tāpiri ia hipanga i te koiora ki waenga i te matū whakahāora me te inenga.

Kei te paparanga tuarua ngā whākōkī ārai-whakahāoratanga e kōkirihia ana e te Nrf2 me te hanganga mitokōria hou. He hōtaka urutau ēnei ka taea te whakaoho e tētahi tukunga perōkai māmā. E whakapae ana ngā kaituhi o te rangahau tiakitanga mitokōria roro ko taua ahotea māmā tonu te kaiwhakaoho, me te kī anō ko te mekameka take mā te Nrf2 e ahu mai ana i ngā rangahau o mua, kaua i tā rātou ake whakaaturanga katoa. Ko te tiakitanga ka tae mai i ngā hāora o muri mā ngā pūmua hou, ehara i te tohu he ārai-whakahāora te matū tīmatanga. Ko tōna tikanga, nā tētahi tūāhua whakatairanga-whakahāoratanga iti i whiwhi ai he ārai nui ake. Ko ngā aratohu mō te pānui i aua kerēme, tae atu ki ngā here o ngā whakamātautau me ngā rerekētanga o ngā takanga, te kaupapa o te aratohu pānui rangahau puru metilīni.

He aha ngā whakamātautau e kore ai e whakaae tētahi ki tētahi

Ka pūrongo tētahi pūoko whānui pērā i te dihydrofluorescein i te whakahāoratanga whānui o te pūoko, ehara i te kukū perōkai. Ka whakawhirinaki ki te matū peroxidase me te heme, ā, ka ngaro pea i a ia tētahi pikinga perōkai ka kitea e tētahi whakamātautau Amplex kua whakatikahia ki te paerewa. I kitea e te rangahau mitokōria roro he perōkai tino teitei ake, engari kāore he tohu superoxide e hāngai ana. He whakatūpato tēnei kia kaua e whakawhirinaki ki tētahi kerēme ārai-whakahāoratanga kotahi e hāngai ana ki te waikano. He pātai mana tika te īnakitanga ā-whatu, nā te mea ka ngongo te waikano i te mārama kitea e tata ana ki ngā awhe whakaoho me ngā awhe tuku mārama e whakamahia nuitia ana. Engari i whakatikahia te rangahau āta whakahaere ki ngā rahinga perōkai mōhiotia, i whakaitihia te pānga mārama whakaoho me te iti noa o te rerekētanga o te tohu, ā, i whakaūngia te pōturi ake o te tangohanga perōkai mā tētahi kawehiko motuhake. Me whakahaere he whakamātautau mana mō te pokanoa, kaua e whakakore aunoa i te hua nā taua take.

Ka whakaatu te hua konupūmā i taua hiahia anō kia tōtika. Kāore te pānga waikano wā-poto i whakarerekē i te kawenga konupūmā katoa i mua i te whakawhitinga uruhanga i te rangahau manawa. Heoi, i pai ake te tere tangohanga konupūmā i ngā mitokōria roro kua āraia i roto i te rangahau mitokōria manawa e aro ana ki te mate huka. He putanga ine rerekē, he pūnaha rerekē, kāore he taupatupatu.

He rārangi arowhai i mua i te whakapono ki tētahi whakatau

Me whakaaro ki ia whakatau ārai-whakahāoratanga, whakatairanga-whakahāoratanga rānei hei pūrongo mō tētahi pūnaha, ā, me pātai e rima ngā pātai. He aha te kukū, ā, kei tēhea wāhi o roto. Ko tēhea te kaituku irahiko, ā, ko tēhea te kaiwhiwhi whakataetae. He mārama, he pōuri rānei, ā, he aha te roangaru me te horopeta. He aha ngā konganuku e wātea ana, ā, he aha ngā puna wahie me ngā puna matū ārai-whakahāoratanga whai rauemi. Ā, ko tēhea te whakamātautau, e ine ana i te rerenga matū whakahāora, i te tūkinotanga, i te urupare urutau rānei. Ki te panoni tētahi whakautu noa iho, ka neke taua rāpoi ngota tonu puta noa i te tūtohi mai i te tiaki ki te tūkino, me te kore rawa he taupatupatu.