▎ 5-Amino-1MQ Numekuku
Nukae nye numekuku si wowɔ le 5-Amino-1MQ ŋu?
Le lãmenugbagbeviwo ƒe lãmesẽ kple agbenɔƒe didi ŋuti numekuku ƒe akpa si le tɔtrɔm me la, dzesidede nu nyui siwo woawɔ atsɔ akpɔ lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxiwo gbɔe eye woahe tsitsi ɖe megbe gakpɔtɔ nye dzɔdzɔmeŋutinunya ƒe nu vevitɔ. Nicotinamide N-methyltransferase (NNMT) ɖea dɔwɔwɔ gã aɖe fiana le ami ƒe lãkusi kple aklã me. To nicotinamide ƒe methylation me la, eɖea eƒe tɔtrɔ zu nicotinamide adenine dinucleotide (NAD+) dzi kpɔtɔna. NAD+ le vevie ŋutɔ na lãmenugbagbeviwo ƒe gɔmedzedze ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ, ŋusẽ wɔwɔ, DNA ɖɔɖɔɖo, kple dzesimɔwo. Eƒe agbɔsɔsɔ nyuitɔ me léle ɖe asi le vevie ŋutɔ na lãmenugbagbeviwo ƒe lãmesẽ kple avuwɔwɔ kple tsitsi kple lãmenugbagbeviwo ƒe dɔmawɔmawɔ nyuie. Le ƒe 2017 me la, numekula siwo le Texas Yunivɛsiti ku nu me zi gbãtɔ le 5-Amino-1MQ ŋu esime wonɔ mɔnu siwo dzi woato axe mɔ ɖe NNMT nu dim. Esi numekulaawo do ƒome sẽŋu si le NNMT kple lolo akpa kple suklidɔ ƒomevi evelia dome ta la, wosusui be mɔxexe ɖe NNMT nu ate ŋu aʋu mɔ yeye siwo dzi woato ada lolo akpa kple eƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxiwo. Esiae nye megbenya vevi si wowɔ na 5-Amino-1MQ numekukua.
Nukae nye dɔwɔwɔ ƒe mɔnu na 5-Amino-1MQ?
Mɔxexe ɖe vidzidɔ me kansa lãmenugbagbeviwo ƒe dzidziɖedzi nu: 5MQ nye mɔxenu sue aɖe si xea mɔ na nicotinamide N-methyltransferase (NNMT) si ɖea ŋusẽ gã aɖe si tsia dzidziɖedzi nu fiana ɖe HeLa epithelial cervical carcinoma cell line dzi, eye ŋusẽkpɔɖeamedzi sia nɔa te ɖe eƒe agbɔsɔsɔme kple ɣeyiɣi dzi. NNMT nye lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlékui si do ƒome kple dɔdzẽ ƒe ŋgɔyiyi kple eƒe kaka. To mɔxexe ɖe NNMT nu me la, anɔ eme be 5MQ gblẽa lãmenugbagbeviwo me lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnu siwo kplɔ wo nɔewo ɖo siwo do ƒome kple dɔdzẽ ƒe tsitsi me. Le kpɔɖeŋu me, 5MQ ate ŋu ado kplamatse dzesimɔ siwo do ƒome kple nicotinamide ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu. Nicotinamide ƒe asitɔtrɔ ƒe masɔmasɔ ate ŋu akpɔ ŋusẽ ɖe lãmenugbagbeviwo ƒe ŋusẽ ƒe asitɔtrɔ, DNA ɖɔɖɔɖo, kple dɔwɔwɔ bubuwo dzi geɖe wu, si ana kansa lãmenugbagbeviwo ƒe dzidziɖedzi natsi. Le dodokpɔwo me la, esi 5MQ ƒe agbɔsɔsɔ dzi ɖe edzi eye atikewɔwɔ ƒe ɣeyiɣi didi la, HeLa lãmenugbagbeviwo ƒe dzidziɖedzi ɖe mɔxexe ɖe enu si dzena vivivi fia. Le ɣeyiɣi ma ke me la, wokpɔ nɔnɔme ƒe tɔtrɔ siwo dometɔ aɖewoe nye lãmenugbagbeviwo ƒe ɖeɖeɖa, lãmenugbagbeviwo dome kadodo ƒe bu, kple apoptotic ŋutilãwo, si ɖee fia be 5MQ hea apoptosis vɛ, si wɔnɛ be lãmenugbagbeviwo ƒe dzidziɖedzi tsia anyi [1]..
Domenyiŋusẽfianu kple Protein ƒe ɖeɖefia si do ƒome kplii ƒe ɖoɖowɔwɔ: Le HeLa lãmenugbagbeviwo ƒe atikewɔwɔ 5MQ megbe la, ZEB1, SIRT1, kple CD16 ƒe mRNA ƒe agbɔsɔsɔ dzi ɖe edzi, gake TWIST kple SERPIN1 mRNA ƒe agbɔsɔsɔ dzi ɖe kpɔtɔ. Le ɣeyiɣi ma ke me la, kansa protein siwo nye phospho-Akt kple SIRT1 ƒe ɖeɖefia dzi ɖe kpɔtɔ. Domenyiŋusẽfianu kple protein siawo wɔa akpa vevi aɖe le dɔdzẽ ƒe dzɔdzɔ kple eƒe ŋgɔyiyi me. Le kpɔɖeŋu me, zi geɖe la, TWIST kple SERPIN1 do ƒome kple dɔdzẽ ƒe amedzidzedze kple dɔdzẽ ƒe kaka. To woƒe ɖeɖefia dzi ɖeɖe kpɔtɔ me la, 5MQ ate ŋu axe mɔ ɖe HeLa lãmenugbagbeviwo ƒe amedzidzedze kple kaka ƒe ŋutete nu. Togbɔ be ZEB1 kple SIRT1 ƒe mRNA ƒe agbɔsɔsɔ dzi ɖe edzi hã la, oncogenic protein SIRT1 ƒe ɖeɖefia dzi ɖe kpɔtɔ. Esia ate ŋu adzɔ elabena 5MQ kpɔa ŋusẽ ɖe nuŋɔŋlɔ megbe ɖoɖowɔwɔ dzi, xea mɔ na SIRT1 protein ƒe dɔwɔwɔ eye wòtoa esia me kpɔa ŋusẽ ɖe lãmenugbagbeviwo ƒe dzidziɖedzi kple agbetsitsi dzi. Akt si me phosphorylate le wɔa akpa vevi aɖe le lãmenugbagbeviwo ƒe agbenɔnɔ, woƒe dzidziɖedzi, kple woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ nyuie me. 5MQ ƒe eƒe ɖeɖefia dzi ɖeɖe kpɔtɔ ate ŋu axe mɔ na kansa lãmenugbagbeviwo ƒe dzidziɖedzi kple agbetsitsi to mɔxexe ɖe dzesimɔ siwo do ƒome kplii nu [1] ..
Nukae nye 5-Amino-1MQ ƒe dɔwɔwɔ?
Le lãmenugbagbeviwo ƒe lãmesẽ ŋuti numekuku me la, eƒe dɔ vevitɔe nye be wòagbugbɔ lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dadasɔ aɖo anyi to mɔxexe ɖe NNMT nu me. NNMT ɖua nicotinamide (si nye NAD+ ƒe ŋgɔdonya) eye wòkpɔa ŋusẽ ɖe methyl nunala ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi, gake 5-Amino-1MQ xea mɔ na dɔwɔwɔ sia: le go ɖeka me la, eɖea nicotinamide methylation zazã le adipocytes me dzi kpɔtɔna, si doa NAD+ ƒe agbɔsɔsɔ ɖe dzi le lãmenugbagbeviwo me be wòana domenyiŋusẽfianu siwo nɔa te ɖe NAD+ dzi (abe SIRT1 ene) nawɔ dɔ nyuie wu mitochondrial function— si nye nusi doa ami ƒe ʋuʋu ɖe ŋgɔ, xea mɔ na ami ƒe dzɔdzɔ, kpena ɖe ŋusẽ ƒe asitɔtrɔ le ami me ŋu, eye wòɖea ami si sɔ gbɔ ɖe lãmekawo me dzi kpɔtɔna. Le go bubu me la, eɖea insulin ƒe dɔlélenutsiŋutete si wokpɔna zi geɖe le lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlélewo me hã dzi kpɔtɔna to insulin ƒe dzesimɔ ƒe seselelãme dzi ɖeɖe kpɔtɔ me, evɔ wòate ŋu aɖɔ aklã me sukli ƒe dzɔdzɔ ɖo le mɔ si mele tẽ o nu be wòakpe ɖe ʋumesukli ƒe agbɔsɔsɔ si li ke ŋu. Gawu la, wole numekuku wɔm le ŋusẽ si wòate ŋu akpɔ ɖe dɔgboa me nugbagbevi suewo dzi ŋu, kple nususugblɔ be ate ŋu ado alɔ lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe homeostasis bliboa le mɔ si mele tẽ o nu to nugbagbevi suewo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi kpɔkpɔ me (le kpɔɖeŋu me, lãmenugbagbeviwo ƒe dɔwɔwɔ si gblẽa nu le ame ŋu dzi ɖeɖe kpɔtɔ).
Le kansa ŋuti numekuku me la, eƒe dɔwɔwɔ ku ɖe taɖodzinu si nye 'metabolic vulnerability' si le tumor cells ŋu. Be dɔdzẽ ƒe lãmenugbagbeviwo nalé dzidziɖedzi kabakaba ɖe te la, zi geɖe la, woɖoa ŋu ɖe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnu siwo mewɔa dɔ le mɔ si mesɔ o nu (abe Warburg ƒe ŋusẽkpɔɖeamedzi ene), eye NNMT dzena le dɔdzẽ ƒe lãmenugbagbevi aɖewo me ŋutɔ, si doa alɔ woƒe lãmenugbagbeviwo ƒe dɔwɔwɔ. To mɔxexe ɖe NNMT nu me la, 5-Amino-1MQ gblẽa dɔdzẽ ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me le mɔ eve nu: Gbã la, eɖea NAD+ ƒe agbɔsɔsɔ si le lãmenugbagbeviwo me dzi kpɔtɔna, si gblẽa ŋusẽ ƒe wɔwɔme me, si wɔnɛ be ŋusẽ kple nugbagbewo ƒe dɔwɔwɔ ƒe nusiwo hiã hena dzidziɖedzi mesɔ gbɔ o; Evelia, egblẽa nu le methyl nunalawo zazã ŋu, si gblẽa epigenetic regulatory processes abe DNA methylation le tumor cells me ene, si wɔnɛ be wòtsia domenyiŋusẽfianu ƒe ɖeɖefia si do ƒome kple dzidziɖedzi kple metastasis nu. Tsɔ kpe ɖe eŋu la, ate ŋu axe mɔ ɖe dɔdzẽ ƒe tsitsi kple kaka nu le mɔ si mele tẽ o nu to asitɔtrɔ le lãmenugbagbeviwo ƒe dɔwɔwɔ ŋu le dɔdzẽ ƒe nuto suea me, si ana gɔmeɖoanyi na numekuku le dɔdzẽ ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe nudede mɔnuwo ŋu me.
Abe numekukudɔwɔnu vevi aɖe ene la, enye mɔnu vevi aɖe si dzi woato aɖe NNMT ƒe ŋutilã ƒe dɔwɔwɔwo gɔme. Numekulawo ate ŋu axe mɔ ɖe NNMT ƒe dɔwɔwɔ nu pɛpɛpɛ to 5-Amino-1MQ zazã me le lãmenugbagbeviwo alo lãwo ƒe kpɔɖeŋuwo me be woalé ŋku ɖe tɔtrɔ siwo kplɔe ɖo le lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dzesiwo me ŋu. Le kpɔɖeŋu me, le lãmenugbagbeviwo ƒe dodokpɔwo me la, ŋkuléle ɖe NAD+ ƒe agbɔsɔsɔ, methyl nunala ƒe agbɔsɔsɔ, kple enzyme siwo kpɔa gome le ami ƒe wɔwɔme me ƒe dɔwɔwɔ ate ŋu ana akpa tɔxɛ si NNMT wɔna le lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me me nakɔ. Le lãwo ƒe kpɔɖeŋuwo me, ne wotsɔe kpe ɖe lãmenugbagbeviwo ƒe kpɔɖeŋuwo me dzodzro ŋu la, enaa woate ŋu adzro NNMT ƒe lãmenugbagbeviwo ƒe dɔwɔwɔwo me—abe ŋusẽ si wòkpɔna ɖe aklã ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi le tsitsime alo ŋusẽ si wònana le ahɔhɔ̃mekawo me ƒe ɖoɖowɔwɔ ene. Gawu la, vovototodedeameme ƒe ŋuɖoɖowo zazã le lãmenugbagbeviwo ƒe hatsotsowo me (le kpɔɖeŋu me, lãmenugbagbevi siwo sɔ siwo ɖea seselelãme sue fiana tsɔ wu ŋuɖoɖo siwo dzena le lãmenugbagbevi siwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ mesɔ o alo esiwo me dɔdzẽ le me) ate ŋu akpe ɖe ame ŋu le lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnu tɔxɛwo gɔmesese me, si afia mɔ numekuku siwo woɖo taɖodzinu na emegbe.
Le lãmekawo ƒe lãmesẽ kple sidzedze ƒe akpawo me la, eƒe dɔwɔwɔ ku ɖe 'ŋusẽ ƒe asitɔtrɔ - lãmenugbagbeviwo ƒe dɔwɔwɔ' ƒomedodo ŋu. Le lãmekawo ƒe lãmesẽ ŋuti numekuku me la, lãmekawo ɖɔɖɔɖo nɔa te ɖe satelait lãmenugbagbeviwo ƒe dɔwɔwɔ kple woƒe dzidziɖedzi dzi, si nye nuwɔna si bia ŋusẽ si sɔ. —5-Amino-1MQ doa satelait lãmenugbagbeviwo ƒe dɔwɔwɔ ɖe ŋgɔ to NAD+ ƒe agbɔsɔsɔ si le lãmenugbagbeviwo me léle ɖe te le lãmekawo me. Le ɣeyiɣi ma ke me la, enaa mitochondria ƒe dɔwɔwɔ nyona ɖe edzi be wòana lãmekawo ƒe ŋusẽ ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu nanyo ɖe edzi, si ɖea nuteɖeamedzi si le hayahaya me le lãmekawo ƒe abixɔxɔ megbe dzi kpɔtɔna. Ate ŋu aɖe oxidative stress si le lãmekawo me hã dzi akpɔtɔ, si akpɔ lãmenugbagbeviwo ta tso nusiwo lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe akpa aɖewo siwo gbɔ eme gblẽna le wo ŋu me. Le sidzedze ŋuti numekuku me la, ahɔhɔ̃mekawo ɖea ŋusẽ si hiã vevie ŋutɔ fiana, eye NAD+ ƒe agbɔsɔsɔ si le ɖiɖim la do ƒome kple ahɔhɔ̃mekawo ƒe dɔwɔwɔ ƒe ɖiɖi. 5-Amino-1MQ kpɔa ahɔhɔ̃mekawo ƒe NAD+ nana ta to mɔxexe ɖe NNMT nu me, to esia me kpɔa mitochondrial ƒe dɔwɔwɔ ta eye wòɖea ahɔhɔ̃mekawo ƒe dɔdzẽ dzi kpɔtɔna. Ate ŋu akpɔ ŋusẽ ɖe ahɔhɔ̃mekawo ƒe asitɔtrɔ hã dzi (to NAD+-dzikpɔkpɔ ƒe enzyme siwo kpɔa gome le ahɔhɔ̃mekawo ƒe wɔwɔme me) be woado alɔ ahɔhɔ̃mekawo ƒe dɔwɔwɔ si do ƒome kple susuŋudɔwɔwɔ (le kpɔɖeŋu me, lãmenugbagbeviwo ƒe dɔwɔwɔ le nusɔsrɔ̃/ŋkuɖodzinutowo me abe hippocampus ene), si ana nukpɔsusu yeyewo na susu ƒe dɔwɔwɔ dzi kpɔkpɔ ŋuti numekuku.
Nyanuwuwuw
Abe nicotinamide N-methyltransferase (NNMT) ƒe mɔxenu tɔxɛ ene la, 5-Amino-1MQ ɖea asixɔxɔ vevi fiana le domenyiŋusẽfianu geɖe me to taɖodzinu ɖoɖo ɖe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔ siwo dzi NNMT kpɔna ŋu. Ate ŋu ana lolo akpa kple insulin ƒe dɔlélenutsiŋutete nanyo ɖe edzi to NAD+ ƒe agbɔsɔsɔ me léle ɖe asi, mitochondria ƒe dɔwɔwɔ nyuie wu, kple lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dadasɔ ake me. Etɔa ŋku lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe gbɔdzɔgbɔdzɔ siwo le dɔdzẽ ƒe lãmenugbagbeviwo me hã, si gblẽa woƒe ŋusẽ wɔwɔ kple domenyiŋusẽfianu ƒe ɖoɖowɔwɔ me be wòaxe mɔ ɖe dɔdzẽ ƒe tsitsi nu. Gawu la, ewɔa dɔ abe numekukudɔwɔnu ene hena NNMT ƒe dɔwɔwɔ me kɔ esime wòle akpa siwo ate ŋu awɔ le lãmekawo ɖɔɖɔɖo kple susuŋudɔwɔwɔ me ɖem fia, si naa mɔfiame veviwo na nudede nyawo me ŋuti numekukuwo le lãmenugbagbeviwo ƒe dɔwɔwɔ, kansa, kple nɔnɔme siwo do ƒome kplii me.
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
Akar s nye numekula si ƒe dɔwɔwɔ ku ɖe molecule ƒe mɔnuwo kple atikewɔwɔ ƒe nudede nyawo me ŋu. Ewɔ akpa aɖe le numekuku siwo ku ɖe akpa si enzymewo kple molecule suewo ƒe mɔxenuwo wɔna le lãmenugbagbeviwo ƒe dzidziɖedzi dzi kpɔkpɔ me ŋu. Eƒe numekukuwo te gbe ɖe alesi wòle vevie be woaɖo taɖodzinu na lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnuwo, abe nicotinamide N-methyltransferase ene, be woaku nugbagbeŋutinunya ƒe mɔnu yeyewo me.Akar s is listed in the reference of citation [2].
