Bya Cocer Peptides 
ennaku 27 eziyise
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okutwalira awamu
Melanotan-1 (MT-1) ye peptide ekola obulungi ennyo (ultra-high-efficiency synthetic melanocyte-stimulating peptide), eddagala erikolebwa mu butonde bw’obusimu obuyitibwa melanocortin, obufunye okufaayo okunene mu by’okwewunda. Melanocortin analogues zikola kinene nnyo mu nkola z’omubiri gw’olususu, nga zikwatagana n’ebikwata ebitongole okulungamya okukola melanin. Melanotan - 1 ekoppa enkola y’obutonde eya melanocortin, n’ekwata ku nkola y’olususu okukola langi, ekikola omusingi gw’okugikozesa mu by’okwewunda.
Ekifaananyi 2 Ensengekera y’eddagala lya Melanotan – 1.
Mu byafaayo, okunoonyereza ku Melanotan-1 kwatandika n’okunoonyereza okw’obwegendereza ku nkola z’okulungamya langi y’olususu. Ng’okunoonya obulungi abantu kweyongera naddala obwetaavu bw’ebikozesebwa mu kulongoosa olususu, abanoonyereza beeyongedde okussa essira ku bintu ebisobola okulung’amya okukola kwa melanin.
Enkola y’Ekikolwa
(1) Okusiba ku bikwata ku Melanocortin
Ekisumuluzo ky’obulungi bwa Melanotan-1 kiri mu busobozi bwayo okwesiba ku melanocortin receptors (MC1R). MC1R ye G protein-coupled receptor okusinga eraga ku ngulu kwa melanocytes. Melanotan-1 bw’ekwatagana ne MC1R, ereeta omuddirirwa gw’ebintu eby’okukyusa obubonero mu butoffaali. Okusiba kuno kukola puloteyina ya G eyungiddwa ku MC1R, nga kino nakyo kikola adenylate cyclase, ekivaako okweyongera mu miwendo gya adenosine monophosphate (cAMP) egy’omubaka owookubiri mu butoffaali. Okulinnya kwa cAMP kwongera okukola protein kinase A (PKA), elung’amya okwolesebwa kw’obuzaale obukwatagana n’okusengejja melanin nga ekola phosphorylating the downstream transcription factor, microphthalmia-associated transcription factor (MITF).
Ekifaananyi 2 Akakwate wakati w’enkyukakyuka esinga obunene mu density ya melanin ne density ya melanin eya baseline ku mukono ogwa waggulu ogw’omunda mu bantu ssekinnoomu aba ITT.
(2) Okulungamya okwolesebwa kw’obuzaale obukwatagana n’okusengejja melanin
MITF nsonga nkulu ey’okuwandiika mu nkola y’okusengejja melanin, esobola okulinnyisa okwolesebwa kw’obuzaale obuwera obuwandiika enziyiza ezikwatibwako mu kukola melanin, nga tyrosinase y’esinga obukulu. Tyrosinase ye enzyme ekoma ku sipiidi mu kukola melanin, ekola okukyusa tyrosine mpolampola okufuuka dopaquinone, oluvannyuma n’ekolebwa okufuuka melanin. Melanotan-1 etumbula emirimu gya MITF, eyongera ku kwolesebwa kwa tyrosinase n’enziyiza endala ezikwatagana n’okusengejja melanin, bwe kityo n’ayanguyiza enkola y’okukola melanin. Melanotan-1 era eyinza okukwata ku kwolesebwa kw’obuzaale obulala obukwatagana n’okusengejja melanin, gamba nga dopa-colorin interconverting enzyme (DCT), n’ebirala. Enziyiza zino zikola mu ngeri ey’okukwatagana okutumbula okukola n’okukuŋŋaanyizibwa kwa melanin, okukkakkana nga langi y’olususu enzirugavu.
(3) Ebikolwa ebikwatagana eby’amakubo g’obubonero mu butoffaali
Ng’oggyeeko ekkubo ly’obubonero erya classic cAMP-PKA-MITF eryogeddwako waggulu, Melanotan-1 era eyinza okulungamya okukola melanin okuyita mu makubo amalala ag’obubonero mu butoffaali. Kiyinza okukwata ku kkubo ly’obubonero eriyitibwa mitogen-activated protein kinase (MAPK). Mu melanocytes, ekkubo ly’obubonero bwa MAPK lyetaba mu kulungamya enkola ez’enjawulo ez’ebiramu nga okukula kw’obutoffaali, okwawukana, n’okuwangaala. Melanotan-1 eyinza okukola ekkubo ly’obubonero bwa MAPK okwongera okutumbula okukula kw’obutoffaali bwa melanocyte n’okukola melanin. Ekkubo ly’obubonero bwa PI3K-Akt era liyinza okuba nga likwatagana n’ebikolwa bya Melanotan-1. Ekkubo lino likola kinene nnyo mu kukula kw’obutoffaali, okuwangaala, n’okulungamya enkyukakyuka mu mubiri, nga liyinza okuwa omusingi gw’enkyukakyuka ogwetaagisa mu kukola melanin nga litereeza enkola z’enkyukakyuka mu butoffaali.
Omulimu mu by'okwewunda
(1) Okutumbula Okulongoosa Olususu
Okwolesebwa kw’ebiva mu kulongoosa enviiri
Ekisinga okweyoleka mu kwewunda kwa Melanotan-1 bwe busobozi bwayo okutumbula okulongoosa olususu. Okunoonyereza kulaga nti oluvannyuma lw’okugaba Melanotan-1 ng’oyita mu mpiso wansi w’olususu oba mu makubo amalala agatuufu ag’okugiwa, okuddugala okw’amaanyi okwa langi y’olususu kuyinza okulabibwa mu bantu. Mu kunoonyereza okwakolebwa abasajja bannakyewa abalamu, empiso ya Melanotan-1 wansi w’olususu ku ddoozi ya 0.08–0.21 mg/kg yassibwa obutasalako okumala ennaku 5 mu wiiki 2 (ddoozi 10). Ebyavudde mu kunoonyereza biraga nti abagezesebwa bafunye langi ya maanyi mu bitundu ng’ekyenyi, emikono n’ensingo. Ekikolwa kino eky’okusiiga enviiri tekiva ku kwonooneka okuva mu UV wabula kiva ku kweyongera kw’okusengejja melanin mu mubiri, ekivaamu langi y’olususu okubeera ey’enjawulo era ey’obutonde.
Ebbanga ly’okukola tanning effect
Enkola y’okusiiga olususu ereetebwa Melanotan-1 erina ekigero ekigere eky’okusigala. Okunoonyereza kwazuula nti ekikolwa ky’okusiiga enviiri kyatuuka ku ntikko nga wayise wiiki emu oluvannyuma lw’okuweebwa, era ne bwe wayise wiiki ssatu nga bamalirizza enkola ya ddoozi kkumi, langi y’olususu yasigala nga nzirugavu nnyo okusinga nga tebannaba kujjanjabwa. Kino kiraga nti Melanotan-1 tekoma ku kutumbula bulungi kukola kwa melanin wabula era nti melanin ekolebwa okuyita mu nkola eno ey’okusengejja esobola okukuumibwa mu lususu okumala ekiseera ekigere, bwe kityo n’eyimirizaawo ekikolwa ky’endabika y’okusiiga.
(2) Ebiyinza okukuuma olususu
Enkola y’okukuuma UV
Melanin akola ng’ekiziyiza eky’obutonde ekikulu eri olususu okuva ku butangaavu bwa UV. Nga eyongera ku kukola melanin, Melanotan-1 mu ndowooza eyongera ku busobozi bw’olususu okunyiga n’okusaasaanya emisinde gya UV, bwe kityo ne kikendeeza ku kwonooneka kw’obutoffaali bw’olususu okuva mu UV. Melanin anywa amaanyi ga UV n’agakyusa ne gafuuka amasoboza ag’ebbugumu okusobola okufulumizibwa, bwe kityo ne kikendeeza ku bulabe bw’okwonooneka okuva mu UV ku macromolecules z’ebiramu nga DNA ne puloteyina. Okugatta ku ekyo, melanin esobola okulungamya abaserikale b’olususu okukendeeza ku buzimba obuva ku UV, n’eyongera okukuuma olususu obutakwonooneka.
Obujulizi bw’okunoonyereza obukwatagana
Newankubadde okunoonyereza mu bujjanjabi ku bikolwa by’okukuuma olususu obutereevu ebya Melanotan-1 mu kiseera kino kutono, obusobozi bwayo obw’okukuuma UV busobola okuteesebwako mu ngeri entuufu okusinziira ku mirimu gy’omubiri egya melanin n’obusobozi bwa Melanotan-1 okutumbula okukola melanin. Okunoonyereza okumu mu vitro kulaga nti melanocytes ezijjanjabiddwa ne Melanotan-1 ziraga emiwendo egya wansi ennyo egy’ebika bya oxygen ebikola (ROS) n’okukendeeza ku miwendo gy’okufa oluvannyuma lw’okukwatibwa UV, ekiraga nti Melanotan-1 eyinza okutumbula okugumiikiriza kw’olususu eri emisinde gya UV ng’eyongera ku kukola melanin.
(3) Ebirala ebiyinza okukosa endabika y’olususu
Okulongoosa mu butonde bw’olususu
Abamu bagamba nti Melanotan-1 ayinza okuba n’akakwate akalungi ku butonde bw’olususu. Okwongera mu kukola melanin kuyinza okutumbula enkyukakyuka y’obutoffaali, okutumbula okukola n’okuzza obuggya kolagini n’ebiwuzi ebiwanvuwa. Mu kunoonyereza okumu okutonotono okwakolebwa mu kwetegereza, abamu ku beetabye mu kunoonyereza kuno baategeeza nti olususu lwabwe lwafuuka lunywevu, lunyirira, era ne balaga okulongoosa mu layini entonotono n’enviiri oluvannyuma lw’okukozesa Melanotan-1. Kino kikwatagana n’okulungamya enkyukakyuka y’olususu ey’ebweru w’obutoffaali nga tuyita mu makubo g’obubonero mu butoffaali agakozesebwa mu kiseera ky’okusengejja melanin.
Okukendeeza ku langi y’olususu
Okunoonyereza okumu era kuzudde nti Melanotan-1 ayinza okuba n’ekikolwa ekimu改善 ku langi y’olususu. Okutondebwa kw’embala y’olususu kitera okukwatagana n’obuzibu mu nkyukakyuka ya melanin. Nga etereeza okukola n’okusaasaana kwa melanin, Melanotan-1 eyinza okuyamba okusaasaanya melanin mu ngeri ey’enkanankana mu lususu, bwe kityo ne kikendeeza ku kulaba kwa langi.
Enkozesa mu kisaawe ky’okulabika obulungi
Oluvannyuma lw’okukuba empiso wansi w’olususu, Melanotan-1 eyingizibwa ddala omubiri, n’eraga obusobozi bw’ebiramu bwe bumu n’okugiwa mu misuwa. Mu kunoonyereza ku ddagala nga tugeraageranya amakubo ag’enjawulo ag’okugiwa, okukuba empiso ya Melanotan-1 wansi w’olususu ku ddoozi za 0.08–0.21 mg/kg kyavaamu ebipimo by’eddagala ebizuulibwa mu plasma, nga ekitundu ky’obulamu bwa plasma kya ssaawa 0.07–0.79 mu kiseera ky’omutendera gw’okunyiga n’essaawa 0.8–1.7 mu kiseera ky’omutendera gwa β. Ebirungi by’okukuba empiso wansi w’olususu mulimu okugigaba mu ngeri ennyangu n’okunyiga eddagala mu ngeri ennywevu; wabula era erina obuzibu obumu, gamba ng’obulumi obuyinza okubaawo mu kitundu, okumyuuka, n’ebintu ebirala ebiyinza okuva mu kifo we bakuba empiso.
4. Okugeraageranya n’Enkola Endala ez’Obulungi
Okugeraageranya n’Enkola z’Ennono ez’okunaaba omusana
Okunaaba omusana mu ngeri ey’ekinnansi nkola ya bulijjo okutuuka ku buzibu bw’okusiiga olususu, naye enkola eno erina ebizibu bingi. Okumala ebbanga eddene ng’olina emisinde gya ultraviolet (UV) kyongera obulabe bwa kookolo w’olususu, okukaddiwa kw’ekitangaala, n’embeera endala, ate era kiyinza okuvaako okwokya omusana, okukala, n’okunyiganyiga. Melanotan-1-induced skin tanning etuukirizibwa okuyita mu kwongera ku endogenous melanin synthesis, mu ndowooza okwewala okwonooneka okuva mu direct UV exposure. Wabula olw’okuba obukuumi bwa Melanotan-1 tebunnaba kuteekebwawo mu bujjuvu, mu kiseera kino tesobola kudda mu kifo ky’okunaaba omusana ogw’ekinnansi ng’enkola ey’okusiiga enviiri etali ya bulabe era eyeesigika.
Okugerageranya n’ebintu ebikolebwa mu kulongoosa enviiri
Waliwo ebintu ebimu ebikolebwa mu kulongoosa olususu ebisangibwa ku katale, gamba ng’ebizigo eby’okwewunda, ebitera okukwatagana ne amino acids ku ngulu ne bikola langi eringa eya langi. Bw’ogeraageranya ne Melanotan-1, ebintu ebikozesebwa mu kulongoosa olususu bikola ku ngulu w’olususu, ekivaamu ebikolwa eby’ekiseera ekitono era biyinza okuleeta ensonga ng’okusiiga langi ezitali za bulijjo oba ezitali za butonde. Ate Melanotan-1 akyusa langi y’olususu okuva munda ng’etereeza enkola ya melanin, ekiyinza okuvaamu ebivaamu ebiwangaala era eby’obutonde.
Mu bufunzi
Nga peptide y’obusimu obusitula obutoffaali obukola omusaayi (synthetic melanocyte-stimulating hormone peptide), Melanotan-1 okusinga ekola nga yesiba ku bikwata obusimu ebisitula melanocyte, okukola amakubo g’obubonero mu butoffaali, n’okulungamya okwolesebwa kw’obuzaale obukwatagana n’okusengejja melanin, bwe kityo n’etumbula okukola kwa melanin. Mu by’okwewunda, kitumbula bulungi okulongoosa olususu n’okunywerera ku ddaala eritali limu, era kiyinza n’okuba n’ebiyinza okukuuma olususu n’ebirala ebirungi ku ndabika y’olususu.
Ensonda
[1] Habbema L, Halk A. B., Neumann M., n’abalala. Obulabe bw’okukozesa mu ngeri etafugibwa alpha-melanocyte-stimulating hormone analogues: okwekenneenya[J]. Ekitabo ky'ensi yonna eky'eby'ensusu, 2017,56 (10): 975-980.DOI: 10.1111 / ijd.13585.
[2] Fitzgerald L. M., Fryer J. L., Dwyer T., n’abalala. Enkola ya MELANOTAN, [Nle (4), D-Phe (7)]-alpha-MSH, ku kukola melanin mu bantu abalina MC1R variant alleles[J]. Peptides, 2006, 27 (2): 388-394.DOI: 10.1016 / j.peptides.2004.12.038.
[3] Ugwu S, Blanchard J, Dorr R, n’abalala. Langi y’olususu n’enkola y’eddagala lya melanotan-I mu bantu[J]. Eddagala ly’ebiramu n’okusaasaanya eddagala, 1997,18:259-269.DOI:10.1002/(SICI)1099-081X(199704)18:33.0.CO;2-X.
Ekintu ekiriwo okukozesebwa mu kunoonyereza kwokka:
