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Mitochondria-Targeted Peptide SS-31 Zazã le Tsitsi Tsitsi Me

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NYATAKAKAWO KPLE NUSIWO WOTSƆ ƑE NYATAKAKA SIWO KAtã WOÐO LE NYATAKAKADZRAÐOƑE SIA ME LA KPLE NYATAKAKAWO kaka KPLEE NUFIAFIA ƑE TAÐOÐOWO KO.  

Wotrɔ asi le atike siwo wona le nyatakakadzraɖoƒe sia ŋu na numekuku le vitro ɖeɖeko. Wowɔa numekuku le vitro (Latingbe me: *le ahuhɔ̃e me*, si gɔmee nye le ahuhɔ̃e me) le amegbetɔ ƒe ŋutilã godo. Atike siawo menye atikewo o, United States ƒe Nuɖuɖu Kple Atike Ŋuti Dɔwɔƒe (FDA) meda asi ɖe wo dzi o, eye mele be woazã wo atsɔ axe mɔ ɖe atikewɔwɔ, dɔléle, alo dɔléle aɖeke nu, adae, alo adae o. Se de se vevie be woatsɔ atike siawo ade amegbetɔ alo lãwo ƒe ŋutilã me le mɔ ɖesiaɖe nu.


Mitochondria-targeted peptide SS-31, si wogayɔna be elamipretide, nye peptide si ƒe molecule sue aɖe si si mitochondria-taɖodzinu ƒe dɔwɔwɔ tɔxɛ aɖe le. Le ƒe ʋɛ siwo va yi me la, esi numekuku siwo wowɔ tso tsitsi ƒe mɔnuwo ŋu va le goglom ɖe edzi la, akpa vevi si mitochondria ƒe dɔmawɔmawɔ nyuie wɔna le tsitsi me va le dzedzem geɖe wu. SS-31, kple eƒe mitochondrial taɖodzinu ƒe nɔnɔme tɔxɛwo kple ŋutete be wòaɖɔ mitochondrial ƒe dɔwɔwɔ ɖo la do ŋugbe na tsitsi ƒe dɔwɔwɔ.


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Nɔnɔmetata 1 Yagbɔgbɔ kple lãkusi ƒe ŋutete ƒe ŋuɖoɖo ɖe ADP ƒe dzodzo ŋu le lãmeka ƒe mitochondria siwo woɖe ɖe aga me hiã cytochrome c kple hexokinase clamp kpeɖeŋutɔ. ADP/ATP ƒe mɔzɔzɔmɔ kple ELAM ƒe kadodo kple ATP Synthase kple ANT.




I. Ƒomedodo si Le Mitochondria Kple Tsitsi Dome Ŋuti Nyatakaka Kpuie


Mitochondria, abe lãmenugbagbevi ƒe ŋusẽtɔ ene, ye wɔa ATP ƒe akpa gãtɔ le lãmenugbagbevi la me eye wokpɔa gome le lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe ɖoɖowɔwɔ kple dzesiwo ƒe tɔtrɔ ƒe ɖoɖo vovovowo hã me. Ne tsitsi le dzidzim ɖe edzi la, mitochondria ƒe dɔwɔwɔ dzi ɖena kpɔtɔna vivivi, si nye tsitsi ƒe dzesi veviwo dometɔ ɖeka. Mitochondria ƒe dɔmawɔmawɔ nyuie dzena le mɔ vovovowo nu, siwo dometɔ aɖewoe nye tɔtrɔ siwo ƒo ƒu ɖe mitochondrial DNA (mtDNA) me, mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe dɔwɔwɔ dzi ɖeɖe kpɔtɔ, si wɔnɛ be ŋusẽ si mesɔ gbɔ o dona; mitochondria ƒe oxygen ƒomevi siwo wɔa dɔ (ROS) ƒe dzidziɖedzi, si hea oxidative stress ƒe nugbegblẽ vɛ, si gagblẽa nu le lãmenugbagbeviwo me biomolecules abe proteins, lipids, kple nucleic acids ene ŋu, si wɔnɛ be lãmenugbagbeviwo ƒe tsitsi kple ku kabakaba. Mitochondria ƒe dɔwɔwɔ si mesɔ o hã gblẽa nu le lãmenugbagbeviwo me calcium homeostasis ŋu, si doa kplamatse lãmenugbagbeviwo ƒe ŋutilã ƒe dɔwɔwɔ nyuie. Tɔtrɔ siawo wɔa dɔ kple wo nɔewo, eye wowɔa tsatsam vɔ̃ɖi aɖe si ƒoa ƒu ʋãa tsitsi ƒe ɖoɖoa.




II. SS-31 ƒe Dɔwɔwɔ ƒe Mɔnu


Mitochondrial Ŋusẽ ƒe Tɔtrɔ ƒe Dɔwɔwɔ ƒe Nyonyome

ADP ƒe Seselelãme ƒe Dzidziɖedzi: Le tsitsi me la, mitochondria ƒe seselelãme ɖe ADP ŋu dzi ɖena kpɔtɔna, si gblẽa nu le ATP ƒe wɔwɔme ƒe ŋutete ŋu. Numekukuwo ɖee fia be SS-31 ate ŋu abla ɖe mitochondrial ADP transporter ANT ŋu tẽ, si ana ANT ƒe ADP ƒe xɔxlɔ̃ nadzi ɖe edzi, si ana mitochondrial ƒe seselelãme ɖe ADP ŋu nadzi ɖe edzi. Le lãmeka ƒe mitochondria tsitsiwo me la, SS-31 dɔdamɔnu dzi ADP ƒe xɔxlɔ̃ ɖe edzi to ANT dzi, si wɔe be mitochondrial gbɔgbɔ le ADP ƒe ʋuʋu te, dzi ATP wɔwɔ ɖe edzi, eye wòna ŋusẽ ƒe asitɔtrɔ le lãmeka ƒe mitochondria tsitsiwo me nyo ɖe edzi.


Mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe ƒuƒoƒo ƒe ɖoɖowɔwɔ: Mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe ƒuƒoƒo nye mitochondrial ƒe ŋusẽ wɔwɔ ƒe akpa veviwo. Le tsitsime la, gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe dɔwɔwɔ dzi ɖena kpɔtɔna zi geɖe. SS-31 ate ŋu alé gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe dɔwɔwɔ ɖe te alo ana woƒe dɔwɔwɔ nanyo ɖe edzi to woƒe wɔwɔme ƒe blibonyenye li ke alo protein siwo do ƒome kplii ƒe ɖeɖefia dzi kpɔkpɔ me. Numekuku siwo wowɔ va yi ɖee fia be le mitochondrial ƒe dɔmawɔmawɔ nyuie ƒe kpɔɖeŋu siwo do ƒome kple tsitsi me la, gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe dɔwɔwɔ gaɖoa wo ɖokui me le SS-31 zazã vɔ megbe, si fia be eƒe ɖoɖowɔwɔ ƒe ŋusẽkpɔɖeamedzi nyui ɖe mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔa dzi.


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Nɔnɔmetata 2 SS-31 ƒe atikewɔwɔ trɔa dzi ƒe tsitsi ƒe nɔnɔmewo


Oxidative stress ƒe nugbegblẽ dzi ɖeɖe kpɔtɔ

ROS wɔwɔ dzi ɖeɖe kpɔtɔ: Mitochondria nye ROS dzɔtsoƒe vevitɔwo dometɔ ɖeka le lãmenugbagbeviwo me, eye ROS wɔwɔ dzina ɖe edzi le mitochondria me le tsitsi me. SS-31 ate ŋu aɖe ROS wɔwɔ dzi akpɔtɔ to mɔ vovovowo dzi. Enaa mitochondrial ŋusẽ ƒe asitɔtrɔ nyona ɖe edzi, si wɔnɛ be mitochondrial elektrɔnik tsɔtsɔ yi teƒe bubuwo ƒe kɔsɔkɔsɔ wɔa dɔ nyuie wu eye wòɖea elektrɔnik ƒe sisi dzi kpɔtɔna, si wɔnɛ be ROS wɔwɔ dzi ɖena kpɔtɔna. SS-31 ate ŋu awɔ dɔ ɖe mitochondrial membrane dzi tẽ, atrɔ eƒe ŋutilãmenɔnɔmewo, aɖe oxidative damage sites le membrane la dzi akpɔtɔ, eye wòaxe mɔ ɖe ROS wɔwɔ nu. Le dzitodzito me lãmenugbagbevi siwo tso sisiblisi tsitsiwo me la, atikewɔwɔ kple SS-31 ɖe mitochondrial ROS ƒe agbɔsɔsɔ dzi kpɔtɔ ŋutɔ, si ɖee fia be ewɔa dɔ nyuie le ROS wɔwɔ dzi ɖeɖe kpɔtɔ me.


Antioxidant enzyme system ƒe ɖoɖowɔwɔ: Antioxidant enzyme system aɖe le lãmenugbagbeviwo me, siwo dometɔ aɖewoe nye superoxide dismutase (SOD), catalase (CAT), kple glutathione peroxidase (GSH-Px), siwo ƒe dɔe nye be woaɖe ROS ɖa. Numekukuwo ɖee fia be SS-31 ate ŋu ana lãmenugbagbeviwo ƒe antioxidant takpɔkpɔ ŋutetewo nadzi ɖe edzi to antioxidant enzyme siawo ƒe ɖeɖefia alo dɔwɔwɔ dzi ɖeɖe kpɔtɔ me. Le lãmenugbagbeviwo ƒe kpɔɖeŋu aɖewo me la, atikewɔwɔ kple SS-31 na SOD kple GSH-Px ƒe dɔwɔwɔ dzi ɖe edzi ŋutɔ, si kpe ɖe eŋu be woaɖe ROS si sɔ gbɔ ɖe lãmenugbagbeviwo me ɖa le ɣeyiɣi nyuitɔ dzi eye wòɖe nusiwo oxidative stress hena vɛ dzi kpɔtɔ.


Mitochondrial membrane ƒe liƒo me léle ɖe asi

Mitochondrial membrane phospholipids ƒe kadodo: SS-31 ƒe wɔwɔme tɔxɛ aɖe si na wòte ŋu blana ɖe mitochondrial membrane ƒe nuto siwo me phosphatidylserine sɔ gbɔ ɖo ŋu wu. Phosphatidylserine nye phospholipid si koŋ na mitochondrial membrane eye wòle vevie ŋutɔ na mitochondrial membrane ƒe wɔwɔme kple dɔwɔwɔ ƒe blibonyenye me léle ɖe asi. Le tsitsime la, phosphatidylserine te ŋu gblẽa nu le oxidative ŋu bɔbɔe, si wɔnɛ be mitochondrial membrane ƒe wɔwɔme kple dɔwɔwɔ mesɔna o. Ne SS-31 bla ɖe phosphatidylserine ŋu vɔ la, ate ŋu akpɔ phosphatidylserine ta tso oxidation me esime wòle mitochondrial membrane ƒe wɔwɔme li ke, si axe mɔ na mitochondrial membrane ƒe ŋutete dzi ɖeɖe kpɔtɔ kple mitochondrial permeability transition pore (mPTP) ƒe ʋuʋu. Dodokpɔ siwo wowɔ le vitro ɖee fia be SS-31 xea mɔ na mitochondrial membrane potential kple mPTP ƒe ʋuʋu si oxidative stress hena vɛ dzi ɖeɖe kpɔtɔ nyuie, si wɔnɛ be mitochondrial membrane ƒe liƒo nɔa anyi.


Protein siwo do ƒome kple lãkusi ƒe ɖoɖowɔwɔ: Protein vovovo siwo kpɔa gome le mitochondria ƒe nusiwo wotsɔ yia teƒe bubuwo, ŋusẽ ƒe asitɔtrɔ, kple dzesiwo ƒe tɔtrɔ me la le mitochondrial membrane me. SS-31 ate ŋu akpɔ ŋusẽ ɖe mitochondrial membrane ƒe liƒo dzi le mɔ si mele tẽ o nu to protein siawo siwo do ƒome kple membrane ƒe dɔwɔwɔ alo woƒe ɖeɖefia dzi kpɔkpɔ me. Ate ŋu aɖɔ anion-mɔ̃ siwo nɔa te ɖe elektrikŋusẽ dzi (VDAC) ƒe dɔwɔwɔ dzi, siwo nye mɔ̃memi ƒe protein vevi siwo le gotagome mitochondrial membrane dzi eye wowɔa akpa vevi aɖe le nusiwo wotsɔ ɖɔa li wo nɔewo kple dzesiwo ƒe kaka le mitochondria kple cytoplasm dome la me léle ɖe asi me. SS-31 ƒe VDAC ƒe ɖoɖowɔwɔ kpena ɖe mitochondrial membrane ƒe dɔwɔwɔ kple liƒo si sɔ ŋu.



 

III. SS-31 ƒe ŋusẽkpɔɖeamedzi tɔxɛwo le tsitsi dzi ɖuɖu me


Ŋusẽ si wòkpɔna ɖe dzitodzito ƒe dɔwɔwɔ dzi

Dzi ƒe dɔwɔwɔ nyuie wu: Dzi nye ŋutinu si hiã ŋusẽ geɖe, eye mitochondria ƒe dɔwɔwɔ le vevie ŋutɔ na dzi ƒe dɔwɔwɔ. Le sisiblisi tsitsiwo gome la, dzia ɖea nya siwo do ƒome kple tsitsi abe diastolic dysfunction ene fiana zi geɖe. Dzɔdzɔmeŋutinunyalawo kpɔe be le SS-31 zazã kwasiɖa 8 megbe la, sisiblisi tsitsiwo ƒe dzi ƒe diastolic dɔwɔwɔ nyo ɖe edzi ŋutɔ. Dɔwɔwɔ nyuie sia kpe ɖe mitochondrial proton ƒe sisi le dzitodzito me lãmenugbagbeviwo me ƒe nɔnɔme si sɔ, mitochondrial ROS ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ, dzitodzito me protein oxidation ƒe agbɔsɔsɔ dzi ɖeɖe kpɔtɔ, kple proteinwo ƒe thiol redox nɔnɔme ƒe tɔtrɔ yi nɔnɔme si dzi ɖe kpɔtɔ wu gbɔ. SS-31 hã dzi cMyBP-C Ser282 ƒe phosphorylation ƒe agbɔsɔsɔ ɖe edzi le dzitodzito me lãmenugbagbeviwo me, si do ƒome kplikplikpli kple dzitodzito ƒe dɔwɔwɔ nyuie wu.


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Nutata 3 Wotsɔ SS31 xe mɔ ɖe nusɔsrɔ̃ ƒe gbɔdzɔgbɔdzɔ le sisiblisi tsitsi siwo alɔ̃madɔmadɔ hena vɛ nu.

 

Ʋukawo takpɔkpɔ: Le tsitsi me la, lãmenugbagbeviwo ƒe dɔwɔwɔ me gblẽna, ʋukawo ƒe ʋuʋu dzi ɖena kpɔtɔna, eye dzitodzito me dɔlélewo te ŋu dzɔna bɔbɔe. Le ʋu suesuesue siwo ʋusɔgbɔdɔ hena vɛ ƒe kpɔɖeŋu si wowɔ le sisiblisi tsitsiwo ƒe ahɔhɔ̃ me me la, atikewɔwɔ kple SS-31 ɖea ʋukawo takpɔkpɔ ƒe ŋusẽkpɔɖeamedzi veviwo fiana. Eɖea mitochondrial free radical wɔwɔ si ʋusɔgbɔdɔ hena vɛ dzi kpɔtɔna, eɖea oxidative stress ƒe nugbegblẽ le ʋukawo ƒe gli ŋu dzi kpɔtɔna, si wɔnɛ be ʋu suesuesuewo ƒe gɔmedzedze hea ɖe megbe ŋutɔ eye wòɖea eƒe dzɔdzɔ dzi kpɔtɔna. Eyata SS-31 wɔa akpa vevi aɖe le ʋukawo ƒe wɔwɔme kple dɔwɔwɔ nyuie me léle ɖe asi kple mɔxexe ɖe ʋukawo ƒe dɔléle siwo do ƒome kple tsitsi me.

Ŋusẽ si wòkpɔna ɖe lãmekawo ƒe dɔwɔwɔ dzi


Sidzedze ƒe dɔmawɔmawɔ nyuie dzi ɖeɖe kpɔtɔ: Ne ƒexɔxɔ le dzidzim ɖe edzi la, lãmekawo ƒe dɔwɔwɔ dzi ɖena kpɔtɔna vivivi, eye susu ƒe dɔmawɔmawɔ nyuie abe ŋkuɖoɖonudzi ƒe dɔmawɔmawɔ nyuie kple nusɔsrɔ̃ ƒe ŋutete dzi ɖeɖe kpɔtɔ ene va nɔa dzedzem geɖe wu. Mitochondrial ƒe dɔmawɔmawɔ nyuie wɔa akpa vevi aɖe le ahɔhɔ̃mekawo ƒe dɔmawɔmawɔ nyuie kple susu ƒe dɔmawɔmawɔ nyuie ƒe gɔmedzedze kple woƒe ŋgɔyiyi me. Le susu ƒe dɔmawɔmawɔ nyuie si isoflurane hena vɛ le sisiblisi tsitsiwo me ƒe kpɔɖeŋu me la, SS-31 ate ŋu atrɔ mitochondrial ƒe dɔmawɔmawɔ nyuie, aɖe susu ƒe dɔmawɔmawɔ nyuie siwo isoflurane hena vɛ. SS-31 doa BDNF ƒe dzesiwo ƒe ɖoɖowɔwɔ ɖe ŋgɔ, etrɔa protein siwo do ƒome kple synaptic plasticity abe synaptophysin, PSD-95, kple p-CREB ene ƒe ɖiɖi ɖe anyi, eye wòdoa NR2A, NR2B, CaMKIIα, kple CaMKIIβ ɖe dzi, si wɔnɛ be synaptic plasticity dzina ɖe edzi eye wòkpɔa susu ƒe dɔwɔwɔ ta.


Alɔ̃madɔmadɔ ƒe nugbegblẽwo dzi ɖeɖe kpɔtɔ: Alɔ̃madɔmadɔ nye nuteɖeamedzi si bɔ, eye ŋusẽ gbegblẽ si wòkpɔna ɖe lãmekawo dzi la gadzena ɖe edzi ne ame tsi, si wɔnɛ be susu ƒe dɔwɔwɔ megawɔa dɔ nyuie o eye ahɔhɔ̃mekawo ƒe dɔmawɔmawɔ nyuie ƒe afɔku dzina ɖe edzi. Le sisiblisi siwo xɔ ɣleti 20 me la, wodo SS-31 (3 mg/kg) to atike si wodona ɖe ŋutigbalẽ te me gbesiagbe hena ŋkeke 4 tsiã ɖe enu, eye wodɔ alɔ̃ gaƒoƒo 4 le ŋkeke eve mamlɛawo dzi. Emetsonuwo ɖee fia be sisiblisi siwo medɔ alɔ̃ o siwo wotsɔ SS-31 da dɔ na la meɖe nusɔsrɔ̃ ƒe ŋutete ƒe gbɔdzɔgbɔdzɔ gã aɖeke fia o, ahɔhɔ̃ me mitochondrial ATP ƒe agbɔsɔsɔ kple synaptic plasticity-regulating proteins gbugbɔ ɖo anyi, eye reactive oxygen species (ROS) kple inflammatory cytokines ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ le hippocampus me. Esia fia be SS-31 ate ŋu aɖe vi le atikewɔwɔ me le alɔ̃madɔmadɔ ɣeyiɣi kpui aɖe ƒe ahɔhɔ̃mekawo ƒe ŋusẽkpɔɖeamedzi gbegblẽ siwo le sisiblisi tsitsiwo ŋu dzi ɖeɖe kpɔtɔ me.


Ŋusẽkpɔɖeamedzi ɖe ayiku ƒe dɔwɔwɔ dzi: Le sisiblisi tsitsiwo ƒe ayiku me la, glomerulosclerosis do ƒome kple mitochondria ƒe gbegblẽ le glomerular epithelial cells me. Le kwasiɖa 8 ƒe SS-31 zazã le mice tsitsi siwo xɔ ɣleti 26 megbe la, SS-31 na mitochondrial ƒe nɔnɔme si do ƒome kple tsitsi nyo ɖe edzi eye wòɖe glomerulosclerosis dzi kpɔtɔ. Etɔxɛe la, eɖe tsitsi ƒe dzesiwo ƒe ɖeɖefia dzi kpɔtɔ (p16, β-Gal si do ƒome kple tsitsi), ena apical epithelial cells ƒe kpekpeme dzi ɖe edzi, eye wòɖe parietal epithelial cell activation ƒe dzesiwo ƒe ɖeɖefia dzi kpɔtɔ (collagen IV, pERK1/2, kple α-smooth muscle actin). Togbɔ be SS-31 mekpɔ ŋusẽ ɖe podocyte ƒe kpekpeme dzi o hã la, eɖe podocyte ƒe gbegblẽ ƒe dzesiwo dzi kpɔtɔ (desmin), ena lãmenugbagbeviwo ƒe blibonyenye nyo ɖe edzi (synaptophysin), eye glomerular endothelial cell density (CD31) si lolo wu kpe ɖe eŋu. Esia fia be SS-31 zazã ɣeyiɣi kpui aɖe hã kpɔa ŋusẽ ɖe glomerular mitochondria dzi eye wònaa glomerular ƒe wɔwɔme nyona ɖe edzi.


Dɔwɔwɔ ɖe ame dzi le lãmenugbagbeviwo ƒe ɖoɖo nu

Lãmenugbagbeviwo ƒe tsitsi hehe ɖe megbe: Le lãmenugbagbeviwo ƒe dodokpɔwo me la, wozã H2O2 tsɔ na tsitsi ƒe kpɔɖeŋu si nuteɖeamedzi hena vɛ le HEK293T lãmenugbagbeviwo me, eye wotsɔ SS-31 de nu eme kplɔe ɖo. Nusiwo do tso eme ɖee fia be SA-β-gal nyui ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ ŋutɔ le SS-31 ƒuƒoƒoa me, si fia be lãmenugbagbeviwo ƒe tsitsi ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ. Tsɔ kpe ɖe eŋu la, lãmenugbagbeviwo me ROS ƒe keklẽŋusẽ dzi ɖe kpɔtɔ, mitochondrial membrane ƒe ŋutete dzi ɖe edzi, eye ATP ƒe agbɔsɔsɔ dzi ɖe edzi le SS-31 ƒuƒoƒoa me. Protein immunoblotting numekuku ɖee fia be P53, P21, kple Acetyl-p53 proteinwo ƒe ɖeɖefia ƒe agbɔsɔsɔme sɔ gbɔ wu le kpɔɖeŋu ƒuƒoƒoa me ne wotsɔe sɔ kple ƒuƒoƒo si me wokpɔa wo gbɔ le, gake SS-31 ƒuƒoƒoa ɖee fia be edzi ɖe kpɔtɔ ne wotsɔe sɔ kple kpɔɖeŋu ƒuƒoƒoa. Le go bubu me la, Sirt1 protein ƒe ɖeɖefia ƒe agbɔsɔsɔme ɖiɖi le kpɔɖeŋu ƒuƒoƒoa me ne wotsɔe sɔ kple ƒuƒoƒo si me wokpɔa wo gbɔ le, gake SS-31 ƒuƒoƒoa ɖe dzidziɖedzi fia ne wotsɔe sɔ kple kpɔɖeŋu ƒuƒoƒoa. Eyata woate ŋu aƒo nya ta be SS-31 ate ŋu ahe HEK293T lãmenugbagbeviwo ƒe tsitsi ɖe megbe to mitochondria ƒe dɔwɔwɔ nyuie wu kple protein siwo do ƒome kple tsitsi ƒe ɖeɖefia le lãmenugbagbeviwo me dzi kpɔkpɔ me.


Takpɔkpɔ tso lãmenugbagbeviwo ƒe gbegblẽ si oxidative stress hena vɛ me: Le ARPE-19 lãmenugbagbeviwo ƒe oxidative stress damage ƒe kpɔɖeŋu si H2O2 hena vɛ me la, atikewɔwɔ kple SS-31 na lãmenugbagbeviwo ƒe agbetsitsi dzi ɖe edzi ŋutɔ, eɖe lãmenugbagbeviwo me ROS ƒe agbɔsɔsɔ dzi kpɔtɔ, eɖe lãmenugbagbevi siwo ƒe mitochondrial membrane ŋutete dzi ɖe kpɔtɔ ƒe agbɔsɔsɔ dzi kpɔtɔ, eɖe PI positivity rate dzi kpɔtɔ ŋutɔ (si ɖe alesi wòkeke tae fia ƒe lãmenugbagbeviwo ƒe ku), eye wòɖe RIP3 protein ƒe ɖeɖefia ƒe dziyiyi dzi kpɔtɔ ŋutɔ. Nusiwo do tso eme siawo ɖee fia be SS-31 kpɔa ame ta vevie tso H2O2 ƒe oxidative stress ƒe nugbegblẽ le ARPE-19 lãmenugbagbeviwo me, si ate ŋu akpe ɖe ame ŋu le tsitsi ƒe nugbegblẽ nu.




Nyanuwuwuw


Peptide SS-31 si woɖo ɖe mitochondria ŋu la kpena ɖe ame ŋu wòtsia tsitsi nu. Tso eƒe ɖoɖowɔwɔ ƒe mɔnu vovovo siwo le mitochondrial ƒe dɔwɔwɔ ŋu dzi va ɖo eƒe ŋusẽkpɔɖeamedzi ɖedzesi siwo tsia tre ɖe tsitsi ŋu le ɖoɖo kple lãmenugbagbeviwo ƒe ɖoƒe vovovowo dzi la, eɖea ŋutete fiana abe tsitsi ƒe mɔnu vevi aɖe ene.




Dzɔtsoƒewo


[1] Patai R, Patel K, Csik B, kple ame bubuwo. Tsitsi, mitochondrial ƒe dɔmawɔmawɔ nyuie, kple ahɔhɔ̃ me ʋu suesuesuewo ƒe dodo: SS-31 (elamipretide) ƒe dodokpɔ do ŋgɔ na dɔdamɔnu kple nɔnɔmetatawo ɖeɖe ƒe mɔ̃ si me wozãa mɔ̃ɖaŋununya tsɔ srɔ̃a nu le si me wowɔa dɔ nyuie le hena ahɔhɔ̃mekawo takpɔkpɔ ƒe atikewɔwɔ ƒe dodokpɔ[J]. Amegãkukuŋutinunya, 2025.DOI: 10.1007 / s11357-025-01634-5.


[2] Farao G, Kamat V, Kannan S, kple ame bubuwo. Peptide elamipretide si woɖo taɖodzinu na le mitochondria me (SS-31) naa ADP ƒe seselelãme nyona ɖe edzi le mitochondria tsitsiwo me to eƒe xɔxlɔ̃ dzi ɖeɖe kpɔtɔ to adenine nucleotide translocator (ANT)[J] dzi. Amegãkukuŋutinunya, 2023, 45 (6): 3529-3548.DOI: 10.1007 / s11357-023-00861-y.


[3] Chiao YA, Zhang H, Sweetweyne M, kple ame bubuwo. Mitochondria ƒe dɔwɔwɔ gbugbɔgaɖoanyi le agbenɔƒe ƒe nuwuwu trɔa dzi ƒe dɔmawɔmawɔ nyuie le mice tsitsiwo me[J]. Elife, 2020,9.DOI: 10.7554 / eAgbe.55513.


[1] Wu J, Dou Y, Ladiges W C. Woxea mɔ na ahɔhɔ̃mekawo ƒe ŋusẽkpɔɖeamedzi gbegblẽ siwo tso alɔ̃madɔmadɔ ɣeyiɣi kpui aɖe me le sisiblisi tsitsiwo me to SS31 Peptide[J]. Gaƒoɖokuiwo & Alɔ̃dɔdɔ, 2020, 2 (3): 325-333.DOI: 10.3390 / gaƒoɖokui alɔ̃dɔdɔ2030024.


[4] Sweetwyne M. T., Pippin J. W., Eng D. G., kple ame bubuwo. Peptide si woɖo taɖodzinu na mitochondrial, SS-31, naa glomerular ƒe xɔtuɖoɖo nyona ɖe edzi le mice siwo tsi wu me[J]. Ayiku Dukɔwo Dome, 2017, 91 (5): 1126-1145.DOI: 10.1016 / j.kint.2016.10.036.


[5] Wu J, Zhang M, Li H, kple ame bubuwo. BDNF mɔa kpɔa gome le SS-31 ƒe ametakpɔkpɔ ƒe ŋusẽkpɔɖeamedzi ɖe isoflurane-si hea susu ƒe dɔmawɔmawɔ nyuie dzi le mice tsitsiwo me[J]. Nuwɔna ƒe ahɔhɔ̃ ŋuti numekuku, 2016, 305: 115-121.DOI: 10.1016 / j.bbr.2016.02.036.

 

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