▎ Liva-g Numekuku
Nukae nye numekuku si wowɔ le Liva-g ŋu?
Free Radical Theory of Aging: Le ƒe 1950-awo me la, Harman do free radical nufiafia si ku ɖe tsitsi ŋu ɖe ŋgɔ, eye wògblɔ be free radicals siwo dona le lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me adze biomolecules dzi, si ana lãmenugbagbeviwo nagblẽ eye woatsi. Nufiafia sia na nukpɔsusu si dzi woanɔ te ɖo awɔ numekuku le nusiwo tsia tsitsi nu ŋu eye wòʋã dzɔdzɔmeŋutinunyalawo be woadi nusiwo ate ŋu axɔ free radicals alo ana lãmenugbagbeviwo ƒe antioxidant ŋutete nadzi ɖe edzi.
Peptide-nu siwo ŋu woke ɖo: Esi dzɔdzɔmeŋutinunyalawo yi edzi le nu gbagbewo ŋuti numekuku deto wɔm ta la, wokpɔe be peptide-nuawo wɔa akpa vevi aɖe le lãmenugbagbeviwo ƒe dzesiwo nana, lãmenugbagbeviwo ƒe dɔwɔwɔ nyuie, kple nu bubuwo me. Dɔ aɖewo le peptide-nu aɖewo ŋu abe antioxidant, anti-inflammatory, kple lãmenugbagbeviwo ɖɔɖɔɖo dodo ɖe ŋgɔ ene, si naa mɔfiame yeye na atike yeye siwo tsia tsitsi nu ƒe wɔwɔ.
Liva-g ƒe Numekuku Kple Eƒe Ŋgɔyiyi: Le nɔnɔme sia me la, Russia dzɔdzɔmeŋutinunyalawo to woƒe numekuku si wowɔ le peptide-nu siwo wotsɔ wɔa peptide ŋu dzi to Liva-g vɛ. Woɖe bioactive peptide kakɛwo tso lãwo ƒe lãkusiwo me eye mlɔeba wokpɔ Liva-g le dodokpɔ kple eƒe nyonyome kplɔ wo nɔewo ɖo megbe. Numekukuwo ɖee fia be Liva-g ate ŋu aɖɔ lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ɖo eye wòana lãmenugbagbeviwo ƒe antioxidant ŋutete nadzi ɖe edzi, si wɔnɛ be lãmenugbagbeviwo ƒe tsitsi nahe ɖe megbe.
Nukae nye Liva-g ƒe dɔwɔwɔ ƒe mɔnu?
1. Ŋusẽkpɔɖeamedzi ɖe Nuɖuɖumeŋusẽ Dzi
Nuɖuɖumeŋusẽ ƒe Dɔwɔnawo Dzi Kpɔkpɔ: Numekukuwo ɖee fia be Liva-g (Lys-Glu-Asp-Ala) nye peptide si me tsi mate ŋu atrɔ o. Peptide hydrolases siwo le dɔgbo suea me mate ŋu awɔ tsi le Liva-g me le mɔ sue aɖe ko nu o [1] . Le in vitro nɔnɔmewo me la, Liva-g ateŋu aɖe glycyl-L-leucine dipeptidase ƒe dɔwɔwɔ le dɔgbo suea me dzi akpɔtɔ 50%. Esi wodo Liva-g na sisiblisiwo kwasiɖa eve vɔ la, nuɖuɖumeŋusẽ ƒe dɔwɔwɔ dzi ɖe kpɔtɔ le lã fẽwo me, evɔ le lã tsitsiwo me ya dzi ɖe edzi. Enyo be míagblɔ be zi geɖe la, enzyme ƒe dɔwɔwɔ le sisiblisi tsitsiwo me le Liva-g xɔxɔ vɔ megbe gogo lãvi siwo le ƒuƒoƒo si me wokpɔa wo gbɔ le ƒe agbɔsɔsɔ [1]..
2. Ŋusẽkpɔɖeamedzi ɖe Enkephalin Degrading Enzymes dzi le Serum me
Inhibiting Enkephalin Degrading Enzymes: Wosrɔ̃ nu tso peptide bioregulators yeye siwo nye Liva-g kple Epi (Ala-Glu-Asp-Gly) ƒe ŋusẽkpɔɖeamedzi ɖe endogenous opioid system dzi ŋu, vevietɔ woƒe ŋutete be woatrɔ enkephalin degrading enzymes ƒe dɔwɔwɔ le serum me eye woawɔ nu kple opioid receptors le ahɔhɔ̃menugbagbeviwo ƒe membrane fraction me. Wokpɔ enkephalinase ƒe dɔwɔwɔ le vitro to ⊃3;H-Leu-enkephalin ƒe tsi ƒe ʋuʋu ƒe agbɔsɔsɔme dzidzedze le dodokpɔ peptideawo ƒe anyinɔnɔ me. Liva-g kple Epi xe mɔ ɖe enzyme siwo gblẽa enkephalin nu le amegbetɔ ƒe ʋumenugbagbeviɣi me nu. Ne wotsɔ Liva-g sɔ kple peptidase mɔxenu nyanyɛwo abe puromycin, leupeptin, kple D-PAM ene la, wokpɔe be ewɔa dɔ wu. Wowɔ Liva-g kple Epi ƒe agbɔsɔsɔme ƒe mɔxexeɖedɔléle ƒe ŋusẽkpɔɖeamedzi ƒe fliwo ƒe nɔnɔmetata, eye woƒe IC55 ƒe asixɔxɔwo nye 20 kple 500 μM [2, 3]..
3. Ametakpɔkpɔ ƒe Ŋusẽkpɔɖeamedzi ɖe Aklãa Dzi
Abe Aklã Takpɔnu Si Ate Ŋu Anye Aklã Takpɔnu ene: Zi geɖe la, atike geɖe zazã le ame tsitsiwo ŋue hea aklã ƒe dɔmawɔmawɔ nyuie vɛ. Eyata ne ame tsi la, afɔku siwo le aklã me fibrotic induration, aklãdɔléle sesẽ kple esi nɔa anyi didi me dzina ɖe edzi. Esia tae wole aklã takpɔnu yeye siwo wɔa dɔ nyuie, eye womegblẽa nu le ame ŋu o dim ɖo. Numekuku aɖewo ɖee fia be aklã me polypeptide complex (Ventvil) kple KEDA tetrapeptide (Lys-Glu-Asp-Ala, Liva-g) ƒe aklã takpɔnu, dɔlélenutsiŋutete takpɔnu, kple tsitsi ƒe ŋutete le wo si. Le lãwo kple le vitro dodokpɔ ƒe kpɔɖeŋu siwo wowɔ le aklãdɔléle ŋu (aklã ƒe fibrotic induration, acute and chronic hepatitis) me la, Ventvil kple KEDA peptide ɖe dɔwɔwɔ nyuie ŋutɔ fia. Ventvil kple KEDA peptide kpɔa ŋusẽ ɖe ame dzi ɣesiaɣi - enaa dɔlélenutsiŋutete kple antioxidant ƒe nɔnɔme nɔa ɖoɖo nu eye wògbugbɔa aklã ƒe dɔwɔwɔ ɖoa anyi le aklãdɔléle me. Numekukuwo ɖee fia be le tsitsi ƒe ɖoɖoa me la, woɖo kpe peptideawo ƒe aklã takpɔkpɔ kple dɔlélenutsiŋutete ƒe ŋusẽkpɔɖeamedzi gãtɔ kekeake dzi [4]..
4. Ŋusẽkpɔɖeamedzi ɖe Lãmetsiŋusẽ ƒe Chromatin dzi
Lãmetsiŋusẽ ƒe Chromatin ƒe Dɔwɔwɔ: Wosrɔ̃ nu tso ŋusẽ si peptide si wowɔ Liva-g kpɔna ɖe ribosomal domenyiŋusẽfianuwo ƒe dɔwɔwɔ dzi, heterochromatin ƒe nɔnɔmetɔtrɔ ƒe nɔnɔmewo, structural C heterochromatin ƒe nɔnɔme vovovowo, kple facultative heterochromatin ƒe tɔtrɔ le ame tsitsiwo ƒe ʋumenugbagbeviɣiwo me ŋu. Liva-g na ribosomal domenyiŋusẽfianuwo wɔ dɔ, heterochromatin si nye constitutive heterochromatin ƒe depolymerization ƒo xlã centromere, kple domenyiŋusẽfianu siwo woxe mɔ na le euchromatin nuto siwo do ƒome kple tsitsi ƒe ƒoƒo ɖe domenyiŋusẽfianuwo me ta la ƒe dodo. Nusiwo do tso eme ɖee fia be Liva-g na woɖe chromatin ƒe deheterochromatization (dɔwɔwɔ) le ame tsitsiwo ƒe domenyiŋusẽfianu me, si wokpɔ to asitɔtrɔ le heterochromatin kple heterochromatinized nuto siwo le domenyiŋusẽfianu me ŋu [5]..
Nukae nye Liva-g ƒe dɔwɔwɔ?
Numekuku le Lãmenugbagbeviwo ƒe Tsitsi Ŋu
Liva-g ate ŋu akpɔ ŋusẽ ɖe enzyme vevi siwo kpɔa gome le lãmenugbagbeviwo ɖɔɖɔɖo alo nuteɖeamedzi ƒe ŋuɖoɖo ƒe mɔnuwo me ƒe dɔwɔwɔ dzi. Le kpɔɖeŋu me, ewɔa nu kple epigenetic regulators eye wòkpɔa ŋusẽ ɖe tɔtrɔ siwo vaa chromatin ƒe wɔwɔme kple domenyiŋusẽfianu ƒe ɖeɖefia ƒe ɖoɖowo me dzi, si wɔnɛ be wòkpɔa lãmenugbagbeviwo ƒe tsitsi ƒe ɖoɖoa dzi. Oxidative ƒe nugbegblẽ ƒoa ƒu le ɣeyiɣi aɖe megbe eye wòhea lãmenugbagbeviwo ƒe dɔmawɔmawɔ nyuie si do ƒome kple tsitsi vɛ. Dɔ si Liva-g kpɔna ɖe oxidative stress mɔ dzi nye numekuku ƒe teƒe veviwo dometɔ ɖeka, eye ate ŋu ahe lãmenugbagbeviwo ƒe tsitsi ɖe megbe to mɔ siwo sɔ la dzi kpɔkpɔ me.
Ŋusẽkpɔɖeamedzi ɖe Aklãdɔlélewo Dzi
Ne ame tsitsiwo le tsitsim la, zi geɖe la, atike geɖe zazã na aklã megawɔa dɔ nyuie o, si wɔnɛ be aklã me ʋu ƒe sisi, aklãdɔléle sesẽ kple esi nɔa anyi didi ƒe afɔkuwo dzina ɖe edzi. Le nɔnɔme sia me la, ele vevie ŋutɔ be woadi aklãtakpɔnu yeye siwo wɔa dɔ nyuie, eye womegblẽa nu le ame ŋu o. Numekuku aɖewo ɖee fia be aklã me polypeptide complex (Ventvil) kple KEDA tetrapeptide (Lys-Glu-Asp-Ala, si nye Liva-g) ƒe aklã takpɔnu, dɔlélenutsiŋutete takpɔnu, kple tsitsi ƒe ŋutete le wo si. Le lãwo ƒe dodokpɔ ƒe kpɔɖeŋu siwo wowɔ le aklã ƒe dɔléle ŋu (aklã ƒe fibrosis, aklãdɔléle sesẽ kple esi nɔa anyi didi) kple dodokpɔ siwo wowɔ le vitro me la, Ventvil kple KEDA peptide ɖe dɔwɔwɔ nyuie ŋutɔ fia. Ventvil kple KEDA peptide wɔa dɔ aduadu, si ate ŋu ana dɔlélenutsiŋutete kple antioxidant ƒe nɔnɔme nasɔ eye wòana aklãa nagawɔ dɔ le aklãdɔléle me. Gawu la, le tsitsi me la, peptide siawo ƒe aklã takpɔnu kple dɔlélenutsiŋutete ƒe ŋusẽkpɔɖeamedzi ɖoa woƒe sesẽƒe [4] ..
Ŋusẽkpɔɖeamedzi ɖe Kansa Dɔnɔwo ƒe Dzɔdzɔmeŋusẽŋununya ƒe Nɔnɔmewo Dzi
Wokpɔe be dɔnɔ siwo ŋu no me dɔdzẽ le ƒe domenyiŋusẽfianu ƒe dzesi enye DNA si me ka ɖeka ƒe gbagbã le fũ, domenyiŋusẽfianu ƒe tɔtrɔ geɖe, kple chromatin ƒe ƒoƒo ɖe enu ƒe agbɔsɔsɔ si dzina ɖe edzi. Oligopeptide bioregulator Liva-g kple cobalt ions zazã abe nusiwo trɔa asi le nu ŋu ene kpɔa ŋusẽ ɖe dɔnɔ siwo ŋu no me dɔdzẽ le ƒe ʋumenugbagbevi dzĩwo ƒe dekɔnuwo ta, si ate ŋu ana nɔnɔme siwo katã ŋu wosrɔ̃ nu tsoe la nasɔ. Esia ɖee fia be to numekuku le dɔnɔ siwo ŋu no me dɔdzẽ le ƒe ʋumenugbagbevi dzĩwo ŋu me la, woate ŋu ada no me dɔdzẽ dɔnɔwo dada ƒe dɔdada ƒe ŋusẽkpɔɖeamedzi kpɔ [6]..
Ŋusẽkpɔɖeamedzi ɖe Dɔnɔ Siwo Ŋu Dzitodzito me Dɔléle Si Gbɔna Kple Woƒe Ƒometɔwo Ƒe Lãmetsiŋusẽ Ŋu
Wosrɔ̃ nu tso ŋusẽ si peptide bioregulator Liva-g (Lys-Glu-Asp-Ala) si wozãna ɖeɖeko kple esi wotsɔ kpe ɖe cobalt ions ŋu kpɔna ɖe nucleolar organizing regions (NORs) ƒe dɔwɔwɔ dzi kple alesi acrocentric chromosomes do ƒome zi geɖe le dɔnɔ siwo ŋu dzitodzito me dɔléle si gbɔ eme le kple woƒe ƒometɔwo ƒe ʋumenugbagbevi dzĩwo me ŋu. Nusiwo do tso eme ɖee fia be Liva-g kple cobalt ions ƒe dɔwɔwɔ ƒokpli dzi NOR ƒe dzidziɖedzi ɖe edzi kple dzesi gã 2 le dɔnɔwo kple woƒe ƒometɔwo me. Atike siawo kpɔ ŋusẽ gã aɖe ɖe acrocentric chromosomes ƒe hadede ƒe dɔwɔwɔ hã dzi, si dze abe dzidziɖedzi gã aɖe le dzesi sia me le numekuku ƒe ƒuƒoƒo eveawo siaa me ene.
Le go sia me la, Liva-g kple cobalt ions ƒe dɔwɔwɔ wɔ dɔ wu. Esi wònye be NORwo ƒe dɔwɔwɔ kple acrocentric chromosomes ƒe hadede zi gbɔ zi geɖe nɔ te ɖe acrocentric chromosomes ƒe aŋgbawo ƒe condensation ƒe nyonyome dzi ta la, woate ŋu aƒo nya ta be Liva-g kple cobalt ions kpɔa ŋusẽ ɖe dɔnɔ siwo ŋu hypertrophic cardiomyopathy le kple woƒe ƒometɔwo ƒe ʋumenugbagbevi dzĩwo dzi, si wɔnɛ be heterochromatinized chromatin ƒe condensation vɛ. Esia ate ŋu anye nɔnɔme si me domenyiŋusẽfianu siwo mewɔa dɔ o ƒe dodo le tsia ƒe ƒoƒo me le numekukua ƒe ƒuƒoƒoa me tɔ ɖekaɖekawo me. Nyatakaka siawo naa nyatakaka yeyewo tso ametakpɔnu si Liva-g kple Liva-g + cobalt ions kpɔna ɖe dɔnɔ siwo ŋu dzitodzito me dɔléle si gbɔ eme le kple woƒe ƒometɔwo ƒe ʋumenugbagbevi dzĩwo dzi ŋu eye ate ŋu akpe ɖe atikewɔwɔmɔnu siwo woato vɛ ŋu [7]..
Ŋusẽkpɔɖeamedzi ɖe Enkephalin Degrading Enzymes dzi le Serum me
Wosrɔ̃ nu tso peptide bioregulators yeye siwo nye Liva-g (Lys-Glu-Asp-Ala) kple Epi (Ala-Glu-Asp-Gly) ƒe ŋusẽkpɔɖeamedzi ɖe opioid ƒe ɖoɖo si le lãmenugbagbeviwo me dzi ŋu, vevietɔ woƒe ŋutete be woatrɔ enkephalin gblẽnu ƒe enzymes ƒe dɔwɔwɔ le ʋumenugbagbeviɣi me eye woawɔ nu kple opioid xɔlawo le ahɔhɔ̃menugbagbeviwo ƒe lãkusi ƒe akpa suea me. Dodokpɔ siwo wowɔ le vitro me de dzesi enkephalinase ƒe dɔwɔwɔ to ⊃3;H-Leu-enkephalin ƒe tsi ƒe ʋuʋu ƒe agbɔsɔsɔme dzidzedze le Liva-g kple Epi ƒe anyinɔnɔ me. Nusiwo do tso eme ɖee fia be Liva-g kple Epi xe mɔ ɖe enzyme siwo gblẽa enkephalin nu le amegbetɔ ƒe ʋumenugbagbeviɣi me nu. Liva-g wɔ dɔ wu peptidase mɔxenu nyanyɛ aɖewo abe puromycin, leupeptin, kple D-PAM ene. Wowɔ Liva-g kple Epi ƒe agbɔsɔsɔme ƒe mɔxexeɖedɔléle ƒe ŋusẽkpɔɖeamedzi ƒe fliwo ƒe nɔnɔmetata, eye woƒe IC5⁄2 ƒe asixɔxɔwo nye 20 kple 500 μM. Wozã radioligand xɔla ƒe mɔnu si me [⊃3;H][D-Ala⊃2;, D-Leu5]-enkephalin le tsɔ da kadodo si le peptideawo kple opioid xɔlawo dome kpɔ. Womekpɔ kadodo aɖeke le μ alo δ opioid xɔla siwo le lãkusi ƒe akpa si le sisiblisi ƒe ahɔhɔ̃ me kple dodokpɔ ƒe peptidewo dome o [2, 3]..
Le nyataƒoƒo me la, to domenyiŋusẽfianu ƒe ɖeɖefia dzi kpɔkpɔ kple protein ƒe wɔwɔme dodo ɖe ŋgɔ me la, Liva-g ɖea ŋusẽkpɔɖeamedzi veviwo fiana le tsitsi nutsitsi, dɔlélenutsiŋutete ƒe tɔtrɔ, kple aklã ƒe dɔwɔwɔ takpɔkpɔ me. Ate ŋu aɖɔ nuɖuɖumeŋusẽ ƒe dɔwɔwɔ ɖo, axe mɔ ɖe enzyme siwo gblẽa enkephalin nu, eye wòahe lãmenugbagbeviwo ƒe tsitsi ɖe megbe to enzyme veviwo ƒe dɔwɔwɔ kple ŋusẽkpɔkpɔ ɖe oxidative stress mɔ dzi me. Gakpe ɖe eŋu la, Liva-g hã nana dɔlélenutsiŋutete ƒe dɔwɔwɔ kple antioxidant ƒe nɔnɔme nyona ɖe edzi to eƒe aklã takpɔkpɔ ƒe ŋusẽ me eye wòdoa aklã ƒe dɔwɔwɔ ƒe hayahaya ɖe ŋgɔ le dɔlélewo abe aklãdɔ ene me. Asixɔxɔ si ate ŋu anɔ eŋu le mɔxexe ɖe dɔléle siwo do ƒome kplii nu kple wo dada me eye wònaa numekuku ƒe mɔfiame yeye aɖe le tsitsi nutsitsi kple lãmesẽ dzi kpɔkpɔ ŋu.
Le Agbalẽŋlɔla La Ŋu
Nusiwo míeyɔ ɖe etame la katã nye esiwo ŋu Cocer Peptides wɔ numekuku le, trɔ asi le wo ŋu eye woƒo wo nu ƒu.
Dzɔdzɔmeŋutinunya ƒe Agbalẽŋlɔla
Vladimir Khavinson nye Russiatɔ ame tsitsiŋutinunyala kple nufialagã xɔŋkɔ aɖe si wonya ɖe eƒe numekuku gbãtɔ le peptide bioregulators kple akpa si wowɔna le tsitsi dzi ɖeɖe kpɔtɔ kple lãmesẽ ƒe nyonyo me ta. Enye St. Petersburg ƒe Nu Gbagbewo Ŋuti Ðoɖowɔwɔ Kple Ame Tsitsiwo Ŋuti Nusrɔ̃ƒe ƒe dɔdzikpɔla eye wònye Russiatɔwo ƒe Dzɔdzɔmeŋutinunya Suku me tɔ si sɔ kplii. Eƒe numekukua ku ɖe atikewɔmɔnu siwo wotu ɖe peptide dzi toto vɛ be woatsɔ ana dɔlélenutsiŋutete ƒe dɔwɔwɔ nanyo ɖe edzi, akpɔ ame ta tso oxidative stress me, eye wòado agbenɔƒe didi ɖe ŋgɔ. Le ƒe blaene me la, eɖe peptide complex gbogbo aɖewo hewɔ wo, si na woto atike ade siwo wotu ɖe peptide dzi kple peptide nuɖuɖu kpeɖeŋutɔ 64 vɛ le atikewɔnyawo me. Khavinson ƒe dɔa kpe ɖe ame tsitsiwo ŋuti nunya ŋu ŋutɔ, vevietɔ le tsitsi ƒe mɔnuwo gɔmesese kple nusiwo woawɔ atsɔ ana ame tsitsiwo ƒe agbenɔnɔ nanyo ɖe edzi la toto vɛ me.
Vladimir Khavinson nye Russiatɔ ame tsitsiŋutinunyala kple nufialagã xɔŋkɔ aɖe, si xɔ ŋkɔ le numekuku yeye si wòwɔ le peptide bioregulators kple akpa si wowɔna le tsitsi dzi ɖeɖe kpɔtɔ kple lãmesẽnyawo dodo ɖe ŋgɔ me ta. Enɔ dɔdzikpɔla ƒe ɖoƒe le St. Petersburg Nu gbagbewo ƒe Dɔwɔnawo Kple Ame Tsitsiwo Ŋuti Nusrɔ̃ƒe eye wònye Russiatɔwo ƒe Dzɔdzɔmeŋutinunya Suku me tɔ si sɔ kplii. Eƒe numekukua ku ɖe atikewɔmɔnu siwo wotu ɖe peptide dzi toto vɛ be woatsɔ ado ŋusẽ dɔlélenutsiŋutete ƒe dɔwɔwɔ, atsi tre ɖe oxidative stress ŋu, eye wòana agbenɔƒe didi nanɔ bɔbɔe ŋu. Le ƒe blaene kple edzivɔ ƒe numekuku me la, eɖe peptide ƒomevi vovovowo hewɔ wo, si do atike ade siwo wotu ɖe peptide dzi kple nuɖuɖu kpeɖeŋutɔ 64 siwo wotu ɖe peptide dzi zazã le atikewɔnyawo me ɖe ŋgɔ. Khavinson ƒe dɔa wɔ akpa vevi aɖe le ame tsitsiwo ŋuti nunya me, vevietɔ le tsitsi ƒe mɔnuwo gɔmesese kple nusiwo woawɔ atsɔ ana ame tsitsiwo ƒe agbenɔnɔ nanyo ɖe edzi la toto vɛ me. Woŋlɔ Vladimir Khavinson ŋkɔ ɖe nyayɔyɔ ƒe nyatakaka me [5].
