Tuhinga
Te kikorangi metilīni i te koiora pūtau: ngā whāinga, ngā tauira, me ngā pānga kua inea
He maha ngā mahi rāpoi ngota o te kikorangi metilīni e tautokona ana e ngā whakamātautau, engari mā te whakarārangi noa i ngā ingoa ara mahi ka kore e mārama he aha tonu tā ia whakamātautau i whakaū ai. He kitenga rerekē te aukati i tētahi whākōkī kua purea, te whakarerekē i te whakapau hāora i roto i ngā pūtau kua whakatipuria, me te whakaiti i tētahi tohu pūmua i te roro kiore. He rerekē ngā whakaritenga whakataurite e hiahiatia ana mō ēnei, ā, he rerekē hoki ngā whakatau e tautokona ana.
Ka whakarōpū tēnei taupū rangahau i aua kitenga mā te tukanga, te tauira, me te putanga ine. Ko te whakaahua uhi e whai mai ana he whakaahua ariā o ngā pūnaha whakamātautau, ehara i te whakatau hanganga rāpoi ngota, i te whakaahua karu whakarahi rānei. Mō te matū kei te pūtake, tīmata ki te matū hāora-whakaheke me ngā tikanga mahi koiora.
Pānuitia ngā tapanga taunakitanga i te tuatahi
Ka whakamātauria e te taunakitanga matū koiora tētahi pūmua, tētahi tauhohenga rānei kua tautuhia, ki waho i tētahi pūtau ora katoa. Ka taea te whakaū i te aukatinga, i te whakawhiti irahiko rānei i raro i ngā āhuatanga kua tohua. Ka tāpirihia e te taunakitanga pūtau te urunga, te pākia, te wehenga ki ngā wāhanga o roto, me ngā ara mahi e pāhekoheko ana. Ka ui te taunakitanga whakawhirinaki mēnā ka whakakorehia te urupare ina tangohia tētahi wāhanga o te ara mahi e whakapaetia ana. Ka ine te taunakitanga rauropi i ngā pānga i roto i tētahi kararehe whai rere toto, whai pākia, whai kiko maha hoki.
E whakaahua ana ēnei tapanga i te pātai kua whakautua, kaua i tētahi raupapatanga kotahi o te kaha taunakitanga. Ka taea e te whakamātautau whakakore ira te tautuhi i tētahi wāhanga tuku tohu e tika ana kia puta ai te urupare, me te kore e whakaatu ka here hāngai te kikorangi metilīni ki taua wāhanga. Ka taea e tētahi hua whanonga kararehe te whakaū i tētahi āhuatanga ka kitea, me te kore e tautuhi i tōna pūtake rāpoi ngota.
He mahere whāinga rāpoi ngota whai hononga
Pānuitia ia rārangi mai i tētahi taha ki tētahi taha. Ka hono te tīwae tuatahi ki te kōrerorero mō te ara mahi; ka tautuhi te hononga rangahau i te pūtake whakamātautau. He mahere tēnei o ētahi taunakitanga matua mō ngā tikanga mahi kua kōwhiria, ehara i te rārangi katoa o ngā pānga pūtau katoa kua pūrongotia.
| Tukanga, whāinga rānei | Pūnaha whakamātautau me te momo taunakitanga | Putanga kua inea me tōna whakamāramatanga |
|---|---|---|
| MAO me te pākia o ngā karere io | MAO-A me MAO-B tangata, he mea hanga mā te hangarau ira, kua purea; ngā tere tauhohenga matū koiora | I ine a Ramsay me ōna hoa i te aukatinga whākōkī. He nui kē atu te tairongo o MAO-A; kāore i inea he putanga mō te wairua, mō te serotonin roro rānei. |
| NOS me te tuku tohu cGMP | Whākōkī waihanga NO kua purea, ngā pūtau o te paparanga o roto o ngā ia toto, ngā ia toto kua wehea; ngā whakamātautau matū koiora me te mahi | I wehe a Mayer me ōna hoa i te hanganga citrulline, te whakaputanga cGMP, me te whakangā. Kāore e taea te tapanga anō i te aukatinga NOS hei aukatinga whiriwhiri i te guanylyl cyclase wairewa. |
| Te kawe irahiko mitokonoria | Ngā pūtau HT-22 hipokamu kiore kua panonitia me ngā tauhohenga matū koiora; ngā taunakitanga pūtau me te matū koiora | I ine a Wen me ōna hoa i te whakapau hāora, te whakawaikawatanga, te ATP, me te whakawhiti irahiko e whakawhirinaki ana ki te hāora-whakaheke. I whakamātauria wehe ēnei putanga. |
| Te karo i te matatini III | Ngā mitokonoria roro kiore kua wehea, me ngā aukati hā pūtau; he whakamātautau wāhanga pūtau | I kitea e tētahi rangahau antimycin mō te matatini III kāore i whakahokia te hā pūtau me te pūmanawa hiko kiriuhi i muri i taua aukatinga, ahakoa i whakahokia ētahi mahi i muri i te aukatinga matatini I. |
| Nrf2 me te hanganga mitokonoria hou | Ngā pūtau hanga muka o ngā kukune kiore momo māori me ērā kua whakakorea te ira Nrf2; te whakawhirinaki ā-ira | I ine a Stack me ōna hoa i ngā tuhinga ira o te urupare ārai hāoratanga. Ko te ngaronga o te whakahohe i ngā pūtau kua whakakorea te ira e tautoko ana i te whakawhirinaki ki Nrf2, kaua i te here hāngai ki Nrf2. |
| Te kai-whaiaro pūtau me te tuku tohu mTOR | Ngā pūtau kura kākano o te hamster Hainamana e whakaputa ana i te tau tangata; ngā whakamātautau pūrongo me te whakaheke whakaputanga ira | I tirotiro a Congdon me ōna hoa i ngā pūrongo LC3, te tāpiri rōpū phosphate ki ngā kinase, me te tau. Nā te whakaheke i te whakaputanga BECN1 i whakakore te urupare whakaheke tau i kitea. |
| Te whakahaere tau me te whakawātea pūmua | He whakamātautau Hsp70 kua purea me ngā pūtau HeLa e whakaputa ana i te tau tangata; ngā taunakitanga matū koiora me te pūtau | I hono a Jinwal me ōna hoa i te aukatinga ATPase ki te hekenga tau e whakawhirinaki ana ki te proteasome. He rerekē tēnei i te ārai i te whakahuihui o ngā muka tau kua purea. |
| Te hanganga kōpūtanga tau | Ngā kōpata tau i hangaia mā te hangarau ira, kua waihangatia anō; he whakamātautau motuhake mō te paitini ki ngā pūtau SH-SY5Y | I ine tētahi rangahau wehenga wāhanga nō 2023 i te hanganga kōpata me te whakakapia hei rā i roto i te ipu whakamātautau, kātahi ka aromatawai i te oranga pūtau mā te MTT i muri i te pānga ki ngā momo tau kua puritia ki ngā āhuatanga whakamātautau. Kāore te whakamātautau pūtau i ine i te hanganga kōpūtanga ki roto i ngā pūtau. |
Ka pupuri te mahere whāinga rāpoi ngota ka taea te tikiake i ngā hononga rangahau taketake, ngā tapanga taunakitanga, me ngā āhuatanga whakamātautau matua ki tētahi tuhinga kuputuhi ka taea te whakamahi anō.
Ngā mea ka wehea e ngā whakamātautau taketake
He horopaki whakamātautau tō te aukatinga whākōkī
I pūrongo te rangahau whākōkī tangata kua purea i tētahi pūmau aukatinga MAO-A, Ki = 27 ± 3 nM, mā te tātari here kaha. Ko tōna IC50 mō MAO-A ko 164 ± 8 nM i raro i ngā āhuatanga whakamātautau kua tohua. Kāore e taea te whakawhiti noa i te Ki me te IC50: ka whakawhirinaki te mea tuarua ki ngā āhuatanga whākōkī me te matū tīmatanga i whakamahia hei ine i te haurua-aukatinga. Ehara tētahi o ēnei tau i te horopeta tangata, i te kukū kiko kua matapaetia rānei.
He whai mōhiohio anō te whakataurite NOS. I ngaro katoa te mahi hanga citrulline i inea i te whākōkī waihanga NO kua purea i te 30 μM kikorangi metilīni. I taua pepa anō, tata ki te 60 μM i hiahiatia mō te haurua-aukatinga o te guanylyl cyclase i whakahohea e te S-nitrosoglutathione. Nō reira, kāore te hekenga o te cGMP pūtau anake e tohu ko te guanylyl cyclase te wāhi o te pānga. Ka whakaata pea i te hekenga o te whakaputanga o te NO e whakahohe ana i taua whākōkī.
Kāore te hā pūtau e ōrite ki te whakaputanga ATP
I te rangahau HT-22, i whakamahia e ngā kairangahau te oligomycin, te FCCP, me te rotenone hei tūhura i te whanonga hā pūtau. I ine motuhake hoki rātou i te ATP. Nā tā rātou matū whakataurite, te FCCP, i whakapiki te whakapau hāora me te whakaheke anō i te ATP pūtau. He whakaaturanga hāngai tēnei i te take kāore e taea e tētahi kauwhata whakapau hāora anake te whakautu i te pātai mō te ATP. Ka whai te aratohu motuhake mō te whakapau hāora hei whakataurite ki te ATP i taua wehewehenga.
I whakamahi ngā mahi o muri mai ki ngā mitokonoria roro kiore kua wehea i ngā matū tīmatanga, tae atu ki te pyruvate me te malate. I te 1 μM, i whakahokia e te kikorangi metilīni tētahi wāhanga o te hā pūtau i aukatihia e te rotenone, engari he iti noa tana mahi i muri i te antimycin. Ka whakawhāiti taua hua i te kerēme whānui e karo tonu ana te waikano i ngā matatini I me III e rua. Me whakaatu te momo rauropi, te whakaritenga mitokonoria, ngā matū tīmatanga, ngā matū aukati, me ngā āhuatanga whakamātautau ki te taha o tētahi hoahoa whakawhiti irahiko e whakaarotia ana.
Ehara te urupare ira i te tohu here hāngai ki te whāinga
I te whakamātautau Nrf2, nā te 0.1, 1, me te 10 μM kikorangi metilīni i whakapiki te tuhinga ira HO1 i ngā pūtau hanga muka o ngā kukune kiore momo māori, engari kāore te urupare i puta i ngā pūtau kua whakakorea te ira Nrf2. He nui ake ngā mōhiohio o tēnei whakataurite ā-ira mō te whakawhirinaki ki te ara mahi i te ine noa i te whakaputanga ira ki ngā pūtau kua pāngia.
Ahakoa tēnā, kāore anō kia whakatauria te takahanga rāpoi ngota nāna i tīmata te urupare. Me noho wehe te tuhinga ira e whakawhirinaki ana ki Nrf2, te hanganga mitokonoria hou, te rerekētanga o te taurite NAD+/NADH, me te tuku tohu AMPK, kia hono rā anō tētahi whakamātautau i aua mea. Kāore te pikinga o te whakaputanga o tētahi ira mitokonoria kotahi e whakaū i hangaia e ngā pūtau he mitokonoria mahi maha ake.
He maha ngā ara whakakore pūmua
I te rangahau kai-whaiaro pūtau, i pāngia ngā pūtau CHO e whakaputa ana i te tau ki te 0.01 μM kikorangi metilīni mō te ono hāora, ā, i whakatauritea ki ngā pūtau i pāngia ki te kawe whakarewa anake. I āwhina tētahi pūrongo LC3 takirua whero/kākāriki ki te wehe i ngā mirumiru o ngā wāhanga tōmua i ngā autolysosome kua whakawaikawatia; nā te bafilomycin i whakarato tētahi āhuatanga whakataurite e whakararu ana i te rere o te tukanga. I whakamātau te whakahekenga whakaputanga BECN1 mēnā i whai wāhi ngā taputapu kai-whaiaro pūtau ki te hekenga tau. Ka hipa ēnei whakamātautau i te tatau noa i ngā ira LC3-pai, ka whakaemi pea ina piki te hanganga, ina pōturi rānei te whakakorenga.
Engari, i tirotiro te rangahau Hsp70 i te mahi ATPase me te whakawātea tau e whakawhirinaki ana ki te proteasome, i roto i tētahi pūnaha pūtau rerekē. He pātai anō tā ngā whakamātautau kōpūtanga nō 2023: he pēhea te hanga kōpata a ngā rāpoi ngota tau, me te panoni i ō rātou āhuatanga ā-rauemi. He putanga ine motuhake te tau katoa, te tau kua tāpirihia he rōpū phosphate, ngā muka kore-wairewa, me ngā kōpūtanga āhua-rā. Mā te whakakotahi i ēnei ki tētahi kerēme “ārai-tau” kotahi ka mukua te tikanga mahi e whakamātauria ana.
Kōwhiria te whakamātautau e whai ake ana mā te wehewehenga e ngaro ana
Mō tētahi pepa hou, tangohia te tuakiri matū pū, te kukū, te roa o te pānga, te whakarewa, ngā āhuatanga whakamārama, te tauira, te mea whakataurite, me te putanga ine i mua i te whakamārama i tōna hoahoa ara mahi. Whakaōritea te whakamātautau ki te kerēme: te hā pūtau ki te rere hā pūtau, te ATP ki te wātea o te pūngao, ngā tere tauhohenga whākōkī ki te aukatinga, me te whakarerekētanga ira ki te whakawhirinaki ki te ara mahi.
Ka kōrero te aratohu horopeta–urupare mō ngā urupare ka huri te ahunga i ngā kukū rerekē. Ka wehe te aratohu ārai hāoratanga me te whakatairanga hāoratanga i te hurihanga hāora-whakaheke i tētahi tapanga ārai hāoratanga mō ngā horopaki katoa. Ka whakamārama te urunga ki ngā pūtau me te wehenga ki ngā kiriuhi he aha te kukū kua tohua i te reo whakatipu kāore ai e ōrite noa ki te pānga o roto i te pūtau; ka whakamārama te rangahau Azure B he aha e kore ai e tika kia whakaarotia ngā momo waikano e whanaunga ana hei mea ka taea te whakawhiti noa.
Kei ngā tuhinga rangahau whānui hoki te mahi caspase, te mate pūtau nā te rino, te tuku tohu mumura, me te koroheketanga pūtau. He ara whai hua ēnei ina ko te putanga ine ko te mate pūtau, te tuku tohu cytokine, te aukatinga tupu mauroa rānei. Ehara ēnei i te taunakitanga tāpiri e puta ana ngā mahi rāpoi ngota katoa ki te pūtau kotahi, i te kukū kotahi. Ka whakatakoto tēnei mahere i ngā ara mā roto i ngā taunakitanga whakamātautau; kāore e huri i aua whakamātautau hei painga haumanu.