Te rerekētanga o te puru metilīni i ngā matū ārai hāoratanga tikanga noa

Kotahi tonu te wā ka tūtaki tētahi matū ārai hāoratanga tikanga noa ki tētahi tuwhena herekore. Ka tuku ia i tētahi irahiko, ka whakakore i te tauhohenga o tana whāinga, ā, ka pau. Ko te tatauranga he kotahi ki te kotahi, ā, ka mutu te whakamarutanga ina pau te tukunga matū.

Kāore te puru metilīni e mahi pēnei. Ka tango ia i ngā irahiko, ka tuku atu, ā, ka hoki ki tōna āhua taketake, kua rite ki te huri taiāwhio anō. Ka taea e te rāpoi ngota kotahi te mahi kia hia mano ngā wā. Mā taua rerekētanga e whakamārama tōna kaha i ngā horopeta iti, me ngā wā kāore i whai hua, ko ērā hoki ngā mea e tino whai akoranga ana. Ka whakataurite te kōrero e whai ake nei i ngā tukanga e rua mā roto i ngā rangahau e toru kua whakaputaina, me te aro tonu ki ngā putanga kore pānga.

He pūnaha whakawhiti, ehara i te hautai

Ko te pūtake matū he takirua āhua ka taea te whakawhiti whakamuri, whakamua hoki. He puru te puru metilīni kua whakahāoratia, he utu hiko tōna, ā, ka memeha ki te wai. Ko te puru metilīni kua whakahekea, e kīia nei ko te leuco-methylene blue, kāore ōna tae, kāore ōna utu hiko, ā, he nui tōna memeha ki te ngako kia whakawhiti noa ai i ngā kiriuhi. I roto i te mitokōria, ka tango te waikano kua whakahāoratia i ngā irahiko i ngā kaikawe e hono ana ki te NADH i te taha tīmatanga o te ara, ka tuku atu ki te cytochrome c me te matatini IV i te taha mutunga. Ka karo tēnei i ngā matatini I ki III, arā, ngā wāhi e tino auau ana te turuturu o ngā irahiko ki te hāora, ka hanga i te superoxide. Ka puta anō te waikano i tōna āhua kua whakahāoratia, ka tukurua i te hurihanga. Kei te tuhinga whakamārama mō te āhua o te mahi a te puru metilīni ngā kōrero mō te mahi a taua takirua.

Ka mahi te matū hopu tuwhena hāngai i muri i te turuturu. Ka tatari kia hangaia te superoxide, te peroxide rānei, kātahi ka whakakore i tōna tauhohenga, kotahi rāpoi ngota mō ia tuwhena. Ka mahi te matū e huri taiāwhio ana i te whakaheke-whakahāora i mua i te turuturu, ka whakatika i te rere o ngā irahiko kia iti iho ai te superoxide e hangaia ana, me te kore e pau. E hāngai ana te tatauranga horopeta ki tēnei: i ngā rangahau kei raro nei, ka mahi te puru metilīni tata ki te 100 nanomolar, engari e hiahiatia ana te 100 micromolar mō te matū hopu tuwhena tikanga noa.

Heoi, kāore te pūnaha whakawhiti e mahi ki te noho takitahi. E whakawhirinaki ana tana mahi ki ngā kaituku me ngā kaitango i ia pito. Ki te whakarerekētia te pūnaha, ka taea e taua rāpoi ngota tonu te tiaki, te kore whai hua, te kore hāngai rānei.

Ngā pūtau io: he whakamarutanga e hiahia ana ki ngā mitokōria e mahi ana

Ko te tino wetewete mārama nō tētahi rangahau hononga hanganga-hohenga i ngā pūtau io HT-22 o te hippocampus. I whakamātauria te puru metilīni me ētahi matū whanaunga e ono ki ngā momo whakararu e whā (Poteet me ōna hoa, 2012). I tiaki te waikano i ngā kukū nanomolar ki te glutamate, te rotenone (he aukati i te matatini I), me te iodoacetate. Ki te glucose oxidase, e whakaputa hāngai ana i te hydrogen peroxide ki te wai whakatipu pūtau, kāore he pānga mai i te 10 nanomolar ki te 10 micromolar, engari i tiaki te pyruvate, he matū hopu tuwhena māmā. Ina ko te whakararu he mekameka irahiko kua pakaru, ka āwhina te pūnaha whakawhiti. Ina kua hangaia kē te peroxide i waho o te pūtau, kāore he mea mā taua pūnaha e kawe.

I whakaatu taua rangahau anō i te take. I tētahi whakamātautau ki te ranunga mitokōria kua wāwāhia, i mahi motuhake ētahi matū whanaunga e rua kāore ō rāua mekameka taha i ngā tūranga 3 me 7, arā, te phenothiazine me te 2-chlorophenothiazine, hei matū ārai hāoratanga hāngai. Kāore te puru metilīni i pērā. I pehi noa ia i te hāoratanga ina noho tahi te NADH me ngā wāhanga mitokōria e mau tonu ana te hanganga. Arā, kāore rawa ia i te hopu tuwhena. He kaikawe ia, ā, me whai te kaikawe i tētahi wāhi tiki utanga me tētahi wāhi tuku.

E rua ngā taipitopito e whakamārama ake ana i tēnei. Nā te tāpiri i tētahi mekameka taha ki te hauota o te mowhiti i te tūranga 10 i heke ai te kaha tiaki ki te kotahi whakamanotanga pea o tōna kaha taketake. I tohu tēnei he tino take te hauota herekore mō te tukanga matū o te hurihanga. Waihoki, nā te pānga roa i piki ai te whakapuakitanga me te hohe o te matatini IV, he urutaunga kāore i whakaputaina e ngā matū whanaunga e hopu hāngai ana i ngā tuwhena. Ko ngā taipitopito e pā ana ki te whakawhiti irahiko i ngā mitokōria he tūāpapa mō te aromatawai i ngā kerēme mō te ārai hāoratanga.

Ngā pūtau kiri: he whakataurite hāngai ka toa te puru metilīni

I whakataurite tētahi atu rangahau i te puru metilīni ki ngā matū ārai hāoratanga e toru kua roa e whakamahia ana, i ngā pūtau fibroblast kiri tangata i tangohia hāngaitia i ngā kaituku hauora, ngā tūroro progeria, me ngā kaituku neke atu i te 80 tau te pakeke (Xiong me ōna hoa, 2017). Mō ngā wiki e whā, i hoatu te puru metilīni i te 100 nanomolar, te N-acetylcysteine i te 100 micromolar, me te MitoQ me te mito-TEMPO i te 100 nanomolar mō ia matū.

He nui te rerekētanga o ngā putanga. I whakaiti te puru metilīni i te superoxide o ngā mitokōria, ā, i tautoko i te whakarea pūtau puta noa i ngā rārangi pūtau. Kāore te N-acetylcysteine i whakaheke i ngā ROS o ngā mitokōria, ā, ko te āhua nei i pōturi ai te whakarea pūtau. I te horopeta MitoQ e whakamahia ana hei paerewa i ngā tuhinga rangahau, i tino piki ngā ROS o ngā mitokōria, ā, i aukatia te whakarea pūtau. I kitea he painga āhua iti o te mito-TEMPO i ētahi rārangi pūtau. O ngā matū e whā, ko te matū whakakōkī e huri taiāwhio ana te mea tino whai hua. Ko te matū ārai hāoratanga kua whakahāngaitia ki tētahi wāhi, e mahi ana mā te ōwehenga rāpoi ngota pūmau, i kino ake ai ngā putanga i te kore whakamahi matū, mō te pānga kotahi marama i tēnei pūnaha.

I tohu ngā kaituhi ko te roanga o te pānga tētahi whakamārama pea, nā te mea i pai ake ngā putanga o ngā pānga MitoQ poto ake i ētahi atu rangahau. Ka hāngai whānui taua here: ka pau ngā matū ārai hāoratanga e mahi ana mā te ōwehenga rāpoi ngota pūmau, ā, ka puta pea he pānga kino i ō rātou hua wāwāhi i ngā whakatipuranga roa. Kāore te matū whakakōkī e pau.

I whakawhānuitia taua hōtaka ki te kiri tangata 3D kua hanga anōtia. I reira, nā te puru metilīni horopeta iti i mātotoru ai te paparanga dermis, i pai ake ai te pupuri wai, i piki ai te elastin me te collagen 2A1, i pehia ai te MMP9, ā, i tere ake ai te kati o ngā patunga. He putanga whakatenatena, engari e pā ana ki te kiri, ā, he rerekē te kiri i te wheua.

Ngā wheua: he putanga whai tūmanako i te rīhi pūtau i ngaro i te kararehe

Kei tērā pito o te whānuitanga o ngā putanga te rangahau mō te kaumātuatanga o te kōhiwi (Poudel me ōna hoa, 2024). I ngā whakatipuranga pūtau, i aukati te puru metilīni me te MitoQ i te hanganga o ngā pūtau wāwāhi wheua, ā, i kaha ake te aukati i te pikinga o te horopeta ki runga ake i te 0.25 micromolar. Kāore i kino te oranga tonutanga o ngā pūtau kakau, te hanganga rānei o ngā pūtau hanga wheua. Ki te pānui te kairangahau i aua whakaaturanga anake, ka matapae ia ka kaha ake ngā wheua o ngā kararehe ka whiwhi i ngā matū.

Kāore ngā putanga kararehe i tautoko i taua matapae. I whiwhi ngā kiore uwha C57BL/6J kua kaumātua i te puru metilīni 250 micromolar i roto i te wai inu mō te 6, te 12 marama rānei. I whiwhi ngā kiore UM-HET3 he kanorau ā-ira i te puru metilīni 28 ppm i roto i te kai mai i te 7 ki te 22 marama te pakeke, i te MitoQ 100 ppm rānei mai i te 4 ki te 22 marama. I whakaatu ngā whakaahua Micro-CT o te wheua kiato o waho me te wheua kōputaputa o roto o te wheua huha, me ngā peke tuaiwi o te hope, he ōrite tonu te haere o te ngaronga wheua e pā ana ki te pakeketanga i ngā rōpū whiwhi matū me ngā rōpū whakahaere. E rua ngā momo kiore, e rua ngā ara tuku, e rua ngā matū ārai hāoratanga, he maha ngā marama o te pānga, kāore he pānga ki te kōhiwi.

He tōtika te whakatau a ngā kaituhi: ko te āhua nei kāore te whakaiti i te taumahatanga hāoratanga mā tētahi matū ārai hāoratanga anake e ranea hei whakaroa i te kaumātuatanga o te kōhiwi. E hono ana te ngaronga wheua ki ngā taiaki, te kawenga ā-tinana, te mumura, me te tango i ngā pūtau kua kaumātua. Ko te whakatika i te turuturu irahiko he whakatika i tētahi take o roto i te tokomaha, ā, i konei ko ērā atu take te mea kaha ake. Ko ngā kōrero mō ngā putanga o ngā rautaki ārai hāoratanga ki ngā āhuatanga kitea o te kaumātuatanga hei horopaki mō tēnei putanga kore pānga.

Te pānui ngātahi i ngā rangahau e toru

E toru ngā tauira e tū tonu ana ina tirohia ngātahitia ngā pepa e toru.

Tuatahi, mā te tukanga e matapae te rohe o te whai hua. Ka āwhina te puru metilīni ina hē te ara o ngā irahiko i roto i ngā mitokōria, ā, ka taea e tētahi kaikawe te whakahuri i tō rātou ara. Kāore e whai hua ina kua hangaia kē ngā matū whakahāora, ā, kei tawhiti i te mekameka. Ko te putanga kore pānga o te glucose oxidase me te putanga kore pānga ki te wheua ehara i te mea whakamā hei kimi whakamārama kia whakakorea atu. E whakaatu ana ēnei i te mahi a te ariā e ai ki ōna whakaritenga.

Tuarua, i raro i te pānga roa, ka pai ake te tatauranga o te whakakōkī i te tatauranga o te ōwehenga rāpoi ngota pūmau. Ka mahi tonu tētahi rāpoi ngota kāore e pau i ngā kukū nanomolar mō ngā wiki, engari ka hiahiatia e ngā matū hopu tuwhena ka pau i te whakamahinga kotahi ngā horopeta rau-micromolar, ā, ka huri pea ki te whakaputa kino i ngā whakatipuranga roa.

Ko ngā kōrero mō te horopeta, te ara tuku, me te tohatoha ki ngā kiko e whakamārama ana i tētahi wāhanga o te take ka huri ai te matū toa i te kukū nanomolar i te whakatipuranga pūtau hei matū kore pānga i roto i te rauropi ora.

Mō ngā mātanga haumanu me ngā kairangahau, he whāiti engari he pakari te whakatau. Ehara te puru metilīni i te matū ārai hāoratanga kaha ake, engari nō tētahi kāwai kē: he kaikawe ka taea te whakahou, e hiahia ana ki ngā mitokōria e mau tonu ana te hanganga, ngā kaituku e wātea ana, me tētahi kaitango i te taha mutunga o te ara. Aromatawaitia ia whakamahinga e whakaarotia ana mā te ui mēnā e noho ana taua ara iahiko i te kiko e whāia ana. Tonoa hoki te whakamātautau whakahaere i mahia i te rangahau a Poteet, arā, he whakararu hāngai mā te peroxide ka taea e te matū hopu tuwhena tūturu te ārai, engari me kore e taea e te kaikawe. Koia hoki te take ka hoki tonu ngā whakataurite a ngā kairangahau mō ngā pūhui hohe whakaheke-whakahāora ki ngā hoahoa whakataurite hāngai.

Ngā puna

Ko ngā whakataurite e toru i runga ake nei nō tētahi rangahau hononga hanganga-hohenga mō te puru metilīni me ōna pärönaki e ono i ngā pūtau io, tētahi whakataurite i ngā matū ārai hāoratanga e whā i ngā pūtau fibroblast kiri tangata me ngā tauira kiri 3D, me tētahi rangahau roa mō te puru metilīni, te MitoQ me te kaumātuatanga o te kōhiwi i ngā momo kiore e rua. E pūrongo ana tēnei tuhinga i ā rātou kitenga, ā, kāore e tuku tūtohutanga maimoatanga.