Cocer Peptides ye ŋlɔe 
ŋkeke 27 enye sia
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.
Kpɔɖeŋu bliboa
Melanotan-1 (MT-1) nye peptide si wowɔ si wɔa dɔ nyuie ŋutɔ si doa ŋusẽ melanocyte, si nye lãmetsi si nye melanocortin si le dzɔdzɔme nu ƒe wɔwɔme, si xɔ ŋkɔ ŋutɔ le atsyɔ̃ɖoɖodɔwɔƒewo. Melanocortin analogues wɔa akpa vevi aɖe le ŋutigbalẽ ƒe ŋutilã ƒe dɔwɔwɔ me, wowɔa dɔ kple receptor tɔxɛwo tsɔ kpɔa melanin ƒe wɔwɔme dzi. Melanotan - 1 srɔ̃a melanocortin ƒe dzɔdzɔme mɔnu, si kpɔa ŋusẽ ɖe ŋutigbalẽa ƒe amadede ƒe dɔwɔwɔ dzi, si nye nusi dzi wotu eƒe zazã le atsyɔ̃ɖoɖodɔwɔƒewo ɖo.
Figure 2 Melanotan ƒe atikewo ƒe wɔwɔme – 1.
Le ŋutinya me la, numekuku tso Melanotan-1 ŋu dze egɔme kple numekuku deto le ŋutigbalẽ ƒe amadede ƒe ɖoɖowɔwɔ ƒe mɔnuwo ŋu. Esi amewo ƒe tugbedzedze didi yi edzi le dzidzim ɖe edzi, vevietɔ ŋutigbalẽ ƒe ŋutigbalẽ ƒe ŋutigbalẽ didi la, numekulawo va le susu hem yi nusiwo ate ŋu ana melanin ƒe wɔwɔme nanyo ɖe edzi ŋu geɖe wu.
Dɔwɔwɔ ƒe Mɔnu
(1) Blanuiléle ɖe Melanocortin Xɔlawo ŋu
Nu vevitɔ si na Melanotan-1 wɔa dɔ nyuie enye ŋutete si le esi be wòabla ɖe melanocortin receptors (MC1R) ŋu. MC1R nye G protein-coupled receptor si woɖena fiana le melanocytes ƒe anyime koŋ. Ne Melanotan-1 bla ɖe MC1R ŋu la, eʋãa lãmenugbagbeviwo me dzesiwo ƒe tɔtrɔ ƒe nudzɔdzɔ vovovowo. Kadodo sia naa G protein si kpe ɖe MC1R ŋu la wɔa dɔ, si hã naa adenylate cyclase wɔa dɔ, si wɔnɛ be lãmenugbagbeviwo me dɔla evelia ƒe tsatsam adenosine monophosphate (cAMP) ƒe agbɔsɔsɔ dzina ɖe edzi. cAMP ƒe dzidziɖedzi ganaa protein kinase A (PKA) si kpɔa domenyiŋusẽfianu siwo do ƒome kple melanin ƒe wɔwɔme ƒe ɖeɖefia dzi to phosphorylation na downstream transcription factor, si nye microphthalmia-associated transcription factor (MITF) me.
Nutata 2 Kadodo si le tɔtrɔ gãtɔ kekeake si le melanin ƒe agbɔsɔsɔ me kple gɔmedzedze ƒe melanin ƒe kpekpeme le abɔta ƒe akpa si le etame ememetɔ le ITT ame ɖekaɖekawo me dome.
(2) Domenyiŋusẽfianu ƒe ɖeɖefia si do ƒome kple melanin ƒe wɔwɔme dzi kpɔkpɔ
MITF nye nuŋɔŋlɔ ƒe akpa vevi aɖe le melanin ƒe wɔwɔme me, si te ŋu doa domenyiŋusẽfianu geɖe siwo ŋlɔa enzyme siwo kpɔa gome le melanin ƒe wɔwɔme me ƒe ɖeɖefia ɖe dzi, eye tyrosinase ye nye vevitɔ kekeake. Tyrosinase ye nye enzyme si xea mɔ na melanin ƒe wɔwɔme, si wɔnɛ be tyrosine trɔna vivivi wòzua dopaquinone, eye emegbe wowɔa esia wòzua melanin. Melanotan-1 doa MITF ƒe dɔwɔwɔ ɖe ŋgɔ, edzia tyrosinase kple enzyme bubu siwo do ƒome kple melanin ƒe wɔwɔme ƒe ɖeɖefia ɖe edzi, si wɔnɛ be melanin ƒe wɔwɔme ƒe ɖoɖoa nɔa kabakaba. Melanotan-1 ate ŋu akpɔ ŋusẽ ɖe domenyiŋusẽfianu bubu siwo do ƒome kple melanin ƒe wɔwɔme, abe dopa-colorin interconverting enzyme (DCT) ene, kpakple bubuwo ƒe ɖeɖefia hã dzi. Enzyme siawo wɔa dɔ aduadu tsɔ doa melanin ƒe wɔwɔme kple eƒe ƒoƒo ɖe ŋgɔ, si wɔnɛ be ŋutigbalẽ ƒe amadede doa viviti mlɔeba.
(3) Lãmenugbagbeviwo me dzesimɔwo ƒe dɔwɔwɔ aduadu ƒe ŋusẽkpɔɖeamedzi
Tsɔ kpe ɖe cAMP-PKA-MITF ƒe dzesimɔ si wonya nyuie si míeyɔ ɖe etame ŋu la, Melanotan-1 ate ŋu aɖɔ melanin ƒe wɔwɔme ɖo to lãmenugbagbeviwo me dzesimɔ bubuwo hã dzi. Ate ŋu akpɔ ŋusẽ ɖe mitogen-activated protein kinase (MAPK) ƒe dzesimɔ dzi. Le melanocytes me la, MAPK ƒe dzesimɔa kpɔa gome le nugbagbewo ƒe dɔwɔwɔ vovovowo abe lãmenugbagbeviwo ƒe dzidziɖedzi, vovototodedeameme, kple agbetsitsi ene dzi kpɔkpɔ me. Melanotan-1 ate ŋu ana MAPK ƒe dzesimɔa nawɔ dɔ be wòagado melanocyte ƒe dzidziɖedzi kple melanin ƒe wɔwɔ ɖe ŋgɔ geɖe wu. PI3K-Akt ƒe dzesimɔ hã ate ŋu ado ƒome kple Melanotan-1 ƒe ŋusẽkpɔɖeamedzi. Mɔ sia wɔa akpa vevi aɖe le lãmenugbagbeviwo ƒe tsitsi, agbenɔnɔ, kple lãmenugbagbeviwo ƒe dɔwɔwɔ dzi kpɔkpɔ me, si ate ŋu ana lãmenugbagbeviwo ƒe gɔmeɖoanyi si hiã na melanin wɔwɔ to lãmenugbagbeviwo me lãmenugbagbeviwo ƒe dɔwɔwɔ dzi kpɔkpɔ me.
Akpa si wòwɔna le Atsyɔ̃ɖoɖo Dɔwɔƒea
(1) Ŋutilã ƒe Ʋuʋudedi Dodo Ðe Ŋgɔ
Tanning ƒe Ŋusẽkpɔɖeamedziwo Ƒe Ðeɖefia
Melanotan-1 ƒe atsyɔ̃ɖoɖo si ɖe dzesi wue nye ŋutete si le esi be wòado ŋutigbalẽ ƒe ŋutigbalẽ ƒe amadede ɖe ŋgɔ. Numekukuwo ɖee fia be ne wodo Melanotan-1 to atike si wodo ɖe ŋutigbalẽ te alo edodomɔnu bubu siwo sɔ dzi vɔ la, woate ŋu akpɔ ŋutigbalẽ ƒe amadede ƒe viviti dodo ɖedzesi aɖe le amesiwo wodo kpɔ me. Le numekuku aɖe si me ŋutsu lɔlɔ̃nu faa dɔwɔla siwo le lãmesẽ me le me la, wodo Melanotan-1 ɖe ŋutigbalẽ te le agbɔsɔsɔ si nye 0.08–0.21 mg/kg me madzudzɔmadzudzɔe ŋkeke 5 le kwasiɖa 2 me (agbɔsɔsɔ 10). Nusiwo do tso eme ɖee fia be lãgbalẽŋudɔwɔnu ɖedzesi aɖe le teƒewo abe ŋgonu, abɔ, kple kɔ ene na amesiwo ŋu wowɔ numekukua le. Menye nusiwo UV gblẽna gbɔe lãgbalẽŋudɔwɔwɔ sia tsona o ke boŋ melanin ƒe wɔwɔme si le lãmenugbagbeviwo me ƒe dzidziɖedzi gbɔe wòtsona, si wɔnɛ be ŋutigbalẽ ƒe amadede nɔa sɔsɔm eye wòle dzɔdzɔme nu wu.
Ɣeyiɣi didi si lãgbalẽŋudɔwɔna ƒe ŋusẽkpɔɖeamedzi
Ŋutilã ƒe ŋutigbalẽ ƒe amadede si Melanotan-1 hena vɛ la nɔa anyi vaseɖe afi aɖe. Numekukuwo ɖee fia be ŋutigbalẽ ƒe amadede ƒe ŋusẽkpɔɖeamedzia ɖo eƒe kɔkɔƒe anɔ abe kwasiɖa ɖeka ene le edodo vɔ megbe, eye le kwasiɖa etɔ̃ le atike ewo zazã vɔ megbe gɔ̃ hã la, ŋutigbalẽa ƒe amadede gakpɔtɔ do viviti wòdze ƒã wu do ŋgɔ na atikewɔwɔ. Esia ɖee fia be menye ɖeko Melanotan-1 doa melanin ƒe wɔwɔ ɖe ŋgɔ nyuie ko o, ke boŋ be woate ŋu alé melanin si wowɔ to wɔwɔme sia me la ɖe ŋutigbalẽa me hena ɣeyiɣi aɖe, si ana ŋutigbalẽa ƒe dzedzeme ƒe ŋusẽkpɔɖeamedzia nanɔ anyi.
(2) Nusiwo ate ŋu akpɔ ŋutigbalẽ ta
UV takpɔnu ƒe mɔ̃
Melanin nye dzɔdzɔmemɔxenu vevi aɖe na ŋutigbalẽa be wòagaxe mɔ ɖe UV keklẽ nu o. To melanin ƒe wɔwɔme dzi ɖeɖe kpɔtɔ me la, le nukpɔsusu nu la, Melanotan-1 doa ŋusẽ ŋutigbalẽa ƒe ŋutete be wòaxɔ UV keklẽwo ahakaka wo, si wɔnɛ be UV-siwo gblẽa nu le ŋutigbalẽ ƒe lãmenugbagbeviwo ŋu dzi ɖena kpɔtɔna. Melanin xɔa UV ŋusẽ eye wòtrɔnɛ wòzua dzoxɔxɔŋusẽ be woaɖee ɖa, si wɔnɛ be afɔku si UV hena vɛ be wòagblẽ nu le nugbagbeviwo ƒe molecule gãwo abe DNA kple proteinwo ene ŋu dzi ɖena kpɔtɔna. Tsɔ kpe ɖe eŋu la, melanin ate ŋu aɖɔ ŋutigbalẽa ƒe dɔlélenutsiŋutete ɖo be wòaɖe dɔdzẽ ƒe ŋuɖoɖo siwo UV hena vɛ dzi akpɔtɔ, si ana ŋutigbalẽa nagakpɔ ta tso nusiwo agblẽ le eŋu me.
Numekuku Kpeɖodzi Siwo Do Ƒome Kplii
Togbɔ be dɔdamɔnu ŋuti numekuku siwo wowɔ tso Melanotan-1 ƒe ŋutigbalẽ takpɔkpɔ tẽ ŋu mesɔ gbɔ fifia o hã la, woate ŋu aƒo nya ta le mɔ si sɔ nu be woate ŋu aƒo nya ta le mɔ si sɔ nu be wòanɔ te ɖe melanin ƒe ŋutilã ƒe dɔwɔwɔ kple Melanotan-1 ƒe ŋutete be wòado melanin ƒe wɔwɔ ɖe ŋgɔ dzi. Numekuku aɖewo siwo wowɔ le vitro ɖee fia be melanocyte siwo wotsɔ Melanotan-1 da dɔe la ɖea oxygen ƒomevi siwo wɔa dɔ (ROS) ƒe agbɔsɔsɔ si bɔbɔ ɖe anyi vie fiana eye apoptosis ƒe agbɔsɔsɔ dzi ɖena kpɔtɔna le UV zazã vɔ megbe, si fia be Melanotan-1 ate ŋu ana ŋutigbalẽ ƒe mɔɖeɖe ɖe UV keklẽ ŋu nadzi ɖe edzi to melanin ƒe wɔwɔme dodo ɖe ŋgɔ me.
(3) Ŋusẽkpɔɖeamedzi bubu siwo ate ŋu akpɔ ɖe ŋutigbalẽ ƒe dzedzeme dzi
Ŋutilã ƒe nɔnɔme si nyo ɖe edzi
Ame aɖewo gblɔ be Melanotan-1 ate ŋu akpɔ ŋusẽ nyui ɖe ŋutigbalẽ ƒe nɔnɔme dzi. Melanin ƒe wɔwɔme si dzi ɖe edzi ate ŋu ana lãmenugbagbeviwo ƒe dɔwɔwɔ nanyo ɖe edzi, si ana collagen kple elastic fibers ƒe wɔwɔme kple wo yeye wɔwɔ nado. Le ŋkuléleɖenuŋu ƒe numekuku sue aɖewo me la, gomekpɔla aɖewo gblɔ be yewoƒe ŋutigbalẽa sesẽna ɖe edzi, tete ŋu nɔa te ɖe enu, eye woɖee fia be fli nyuiwo kple flitetewo nyo ɖe edzi le Melanotan-1 zazã vɔ megbe. Esia do ƒome kple ŋutigbalẽ ƒe lãmenugbagbeviwo godo ƒe matriki ƒe asitɔtrɔ to lãmenugbagbeviwo me dzesimɔ siwo wɔa dɔ le melanin ƒe wɔwɔme me dzi.
Ŋutilã ƒe amadede dzi ɖeɖe kpɔtɔ
Numekuku aɖewo hã de dzesii be Melanotan-1 ate ŋu akpɔ ŋusẽ aɖe ɖe ŋutigbalẽ ƒe amadede dzi. Zi geɖe la, ŋutigbalẽ ƒe amadede ƒe wɔwɔme do ƒome kple dɔléle siwo le melanin ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me. To melanin ƒe wɔwɔme kple eƒe mama dzi kpɔkpɔ me la, Melanotan-1 ate ŋu akpe ɖe eŋu be melanin nama ɖe ŋutigbalẽa me sɔsɔe, si ana amadede ƒe dzedzeme naɖe akpɔtɔ.
Dɔwɔwɔ le atsyɔ̃ɖoɖo ƒe akpa dzi
Le atike si wodo ɖe ŋutigbalẽ te megbe la, Melanotan-1 xɔa ŋutilãa keŋkeŋ, eye wòɖea nugbagbewo ƒe dɔwɔwɔ fiana abe alesi wodoe ɖe ʋuka me ene. Le atikewo ƒe dɔwɔwɔ ŋuti numekuku aɖe si me wotsɔ mɔ vovovo siwo dzi woato adoe sɔ kple wo nɔewo me la, Melanotan-1 dodo ɖe ŋutigbalẽ te le agbɔsɔsɔ si nye 0.08–0.21 mg/kg me na be woate ŋu akpɔ atike ƒe agbɔsɔsɔ le ʋumenugbagbevi dzĩ me, eye ʋumenugbagbeviɣi ƒe afã ƒe agbenɔƒe nye gaƒoƒo 0.07–0.79 le eƒe absorption ƒe akpaa me eye gaƒoƒo 0.8–1.7 le β ƒe akpaa me. Viɖe siwo le atike si wodona ɖe ŋutigbalẽ te ŋu dometɔ aɖewoe nye atike si wodona bɔbɔe vie eye wòxɔa atike si li ke; ke hã, seɖoƒe aɖewo hã le eŋu, abe vevesese si ate ŋu anɔ teƒea, abibibi, kple nu bubu siwo ate ŋu ado mo ɖa le afisi wodoe ɖo ene.
4. Tsɔtsɔ Sɔ Kple Atsyɔ̃ɖoɖo Mɔnu Bubuwo
Ne wotsɔe sɔ kple Ɣe ƒe Kɔkɔe ƒe Mɔnu Siwo Wotsɔna Klɔa Ɣe
Ɣe ƒe keklẽ si wozãna le blema nye mɔnu si bɔ si dzi woato akpɔ ŋutigbalẽ ƒe ŋutigbalẽ ƒe amadede, gake kuxi geɖe le mɔnu sia ŋu. Ultraviolet (UV) keklẽŋusẽ zazã ɣeyiɣi didi nana ŋutigbalẽ me kansa, foto ƒe tsitsi, kple nɔnɔme bubuwo ƒe afɔkua dzina ɖe edzi, evɔ ate ŋu ana ŋdɔkutsu dzatsɛ, ƒuƒuiƒe, kple flitete hã nava. Wokpɔa ŋutigbalẽ ƒe lãgbalẽ si melanotan-1 hena vɛ to melanin ƒe wɔwɔme si dzina ɖe edzi le lãmenugbagbeviwo me, si le nukpɔsusu nu la, woƒoa asa na nusiwo UV-ƒoƒo tẽ hena vɛ. Gake esi womeɖo kpe Melanotan-1 ƒe dedienɔnɔ dzi bliboe haɖe o ta la, fifia mate ŋu axɔ ɖe ŋdɔkutsu dzatsɛ si wozãna tsã teƒe keŋkeŋ abe lãgbalẽŋudɔwɔnu si le dedie eye kakaɖedzi le eŋu ene o.
Ne wotsɔe sɔ kple Atike Siwo Wotsɔ Wɔ Lãgbalẽe
Atike aɖewo li siwo wotsɔ lãgbalẽ wɔe le asi me, abe atike siwo wotsɔna ɖaa ŋutigbalẽa ene, siwo zi geɖe la, wowɔa dɔ kple amino acid siwo le ŋutigbalẽa dzi tsɔ wɔa amadede si le abe lãgbalẽ ene. Ne wotsɔe sɔ kple Melanotan-1 la, lãgbalẽŋudɔwɔnu siwo wowɔ kple asi wɔa dɔ ɖe ŋutigbalẽa ƒe gowo dzi, si wɔnɛ be ewɔa dɔ ɖe ŋutigbalẽa dzi ɣeyiɣi kpui aɖe ko eye ate ŋu ahe nyawo abe amadede si mesɔ o alo esi mele dzɔdzɔme nu o ene vɛ. Gake melanotan-1 ya trɔa ŋutigbalẽ ƒe amadede tso ememe to melanin ƒe wɔwɔme dzi kpɔkpɔ me, si ate ŋu ana nusiwo nɔa anyi didi wu eye wole dzɔdzɔme nu.
Nyanuwuwuw
Abe lãmetsiŋusẽ ƒe peptide si wowɔ si doa ŋusẽ melanocyte ene la, Melanotan-1 wɔa dɔ koŋ to kadodo kple lãmetsiŋusẽxɔla siwo doa ŋusẽ melanocyte, lãmenugbagbeviwo me dzesimɔwo ƒe dɔwɔwɔ, kple domenyiŋusẽfianu siwo do ƒome kple melanin ƒe wɔwɔme ƒe ɖeɖefia dzi kpɔkpɔ, si wɔnɛ be wòdoa melanin ƒe wɔwɔ ɖe ŋgɔ me. Le atsyɔ̃ɖoɖo gome la, edoa ŋutigbalẽ ƒe ŋutigbalẽ ƒe amadede ɖe ŋgɔ nyuie kple alesi wònɔa anyi ɖaa, eye ate ŋu akpɔ ŋutigbalẽ takpɔkpɔ kple ŋusẽkpɔɖeamedzi nyui bubuwo hã ɖe ŋutigbalẽ ƒe dzedzeme dzi.
Dzɔtsoƒewo
[1] Habbema L, Halk A. B., Neumann M., kple ame bubuwo. Afɔku siwo le alpha-melanocyte-stimulating hormone analogues zazã si ŋu womewɔ ɖoɖo ɖo o me: numetoto[J]. Dukɔwo Dome Nyadzɔdzɔgbalẽ si Ku Ðe Ŋutilãŋutinunya Ŋu, 2017,56 (10): 975-980.DOI: 10.1111 / ijd.13585.
[2] Fitzgerald L. M., Fryer J. L., Dwyer T., kple ame bubuwo. Ŋusẽ si MELANOTAN, [Nle(4), D-Phe(7)]-alpha-MSH, kpɔna ɖe melanin ƒe wɔwɔme dzi le amegbetɔ siwo si MC1R ƒe alleles vovovowo le me[J]. Peptides, 2006, 27 (2): 388-394.DOI: 10.1016 / j.peptides.2004.12.038.
[3] Ugwu S, Blanchard J, Dorr R, kple ame bubuwo. Ŋutilã ƒe amadede kple atikewo ƒe dɔwɔwɔ le melanotan-I me le amegbetɔwo me[J]. Atikewɔwɔ kple atikewo zazã, 1997, 18: 259-269.DOI: 10.1002 / (SICI) 1099-081X (199704) 18: 33.0.CO; 2-X.
Adzɔnu si li na numekuku zazã ɖeɖeko:
