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1kits (Ebipipa 10) .
| Omuwendo: | |
|---|---|
▎ ya Melanotan-2 Enzimba
Ensibuko: PubChem |
Omutendera: Ac-Nle-cyclo (Asp-His-D-Phe-Arg-Trp-Lys)-NH2 Ensengekera ya molekyu: C 50H 69N 15O9 Obuzito bwa molekyu: 1024.2 g/mol Ennamba ya CAS: 121062-08-6 PubChem CID: 92432. Omuntu w’abantu Ebigambo ebifaanagana: MT-II |
▎ Okunoonyereza ku Melanotan-2
Ensibuko y'okunoonyereza ku Melanota eri etya ?
Melanota ye analogu ey’obutonde (synthetic analogue). Ye analogu y’obutonde eya α-melanocyte-stimulating hormone (α-MSH), ekolebwa mu nkola z’okusengejja eddagala [1] . α-MSH busimu obubeera mu butonde era nga bulina emirimu egy’enjawulo egy’omubiri mu mubiri gw’omuntu, omuli okulung’amya langi y’olususu. Melanota yategekebwa okukoppa ebimu ku bikolwa bya α-MSH naye ng’erina emirimu egy’amaanyi n’ebigendererwa ebitongole eby’okukozesa. Melanota yasooka kukolebwa ng’ekintu ekiyamba okutumbula langi y’olususu, kwe kugamba, ekiyitibwa ekirungo ekifuula olususu. Olw’obwetaavu bw’abantu obw’okusiiga enviiri okweyongera, abantu abamu baatandika okunoonya okufuna ekirungo ekiddugala amangu olususu nga bakuba empiso ya Melanota . Okunoonyereza ku nsonga eno okusinga kussa essira ku nkola yaayo n’engeri gye kikwata ku langi y’olususu. Okugeza, okunoonyereza kuzudde nti Melanota esobola okwesiba ku bikwata ebitongole ku melanocytes okusitula okukola melanin, bwe kityo n’eddugala olususu [2, 3]..
Melanota kye ki ?
Melanota ye analogu ey’obutonde ekwatagana n’obusimu obusitula obutoffaali obuyitibwa α-melanocyte-stimulating hormone (α-MSH). Omulimu gwayo omukulu kwe kwongera langi y’olususu n’okuddugala olususu lw’omuntu. Melanota okusinga ekola ekikolwa kyayo nga ekwatagana n’ebikwata melanocortin. Okusingira ddala, nga non-selective melanocortin receptor agonist, esobola okusitula okukola melanin mu lususu, bwe kityo ne kituuka ku langi y’olususu, kwe kugamba, ekikola ku kulongoosa. Ng’oggyeeko ekyo, era esobola okuvaamu okusituka kw’obusajja mu ngeri eyeetongodde n’okusitula okwegatta.
Enkola ki entongole eya Melanota mu kulongoosa enviiri?
Melanota ereeta olususu okuzimba nga ekwatagana n’ekirungo kya melanocortin 1 ku melanocytes. Kiteeberezebwa nti Melanota ekoppa enkola ya melanocortin α-melanocyte-stimulating hormone (α-MSH) ku MC1 receptor ya melanocytes, ekivaamu okweyongera mu kwolesebwa kwa agouti signaling protein. Melanota esitula melanocytes okukola n’okufulumya melanin, bwe kityo ne kyongera ku langi y’olususu [4] . Kiyinza okutumbula okukola eumelanin mu lususu okutuuka ku langi y’olususu. Okunoonyereza kulaga nti α-melanocyte-stimulating hormone (α-MSH) analogue cyclic -[Ac-Nle(4), Asp(5), D-Phe(7), Lys(10)] alpha-MSH-(4 - 10) amide (Melanota ), ekirungo eky’amaanyi ekiziyiza melanocortin receptor, kisobola okusitula okukola eumelanin okutuuka ku langi y’olususu [5] . .
Enkola ki entongole Melanota gy’ekola mu kuleetera obusajja okusituka n’okutumbula okusikirizibwa kw’okwegatta?
Okuyingiza omuntu okusituka:
Mu nvunza ezabuzibwabuzibwa, Melanota —a non-specific melanocortin receptor agonist —yalaga dose-dependent erectile induction bwe yaweebwa okuyita mu mpiso mu misuwa (0.1-1 mg/kg) oba hypothalamic paraventricular nucleus infusion (0.1-1 μg). Ekikolwa kino kyavaako okusituka kw’obusajja era ne kikendeeza ku kusirika kw’ebintu ebisooka eby’okusituka [6] .Ekikolwa kyayo kiyinza okuzingiramu okukola ebikwata melanocortin mu nkola y’obusimu ey’omu makkati, bwe kityo ne kitereeza amakubo g’obusimu agakwatagana n’okusituka. Melanota bw’efukibwa mu nnyindo (0.2 μg) ku ddaala lya L6 - S1, amplitude y’ebintu ebibaawo mu kusituka eba waggulu. Kino kiraga nti amakubo g’obusimu ku ddaala ly’omugongo nago gayinza okwenyigira mu kuleeta okusituka kwa Melanota [6]..
Okutumbula okusituka:
Oluvannyuma lw’okukuba empiso ya Melanota mu misuwa (1 mg/kg), okuddamu kw’okusituka okuleetebwa okusikirizibwa kw’obusimu obuyitibwa cavernous nerve stimulation kweyongera, bwe kityo ne kikola omulimu ogw’okutumbula mu kusituka [6] . Oluvannyuma lw’okuggyawo amangu olujegere lw’okusaasira oluyitibwa lumbar paravertebral sympathetic chain, ekikolwa eky’okutumbula ekya Melanota kiggyibwawo. Kino kiraga nti okutumbula ekikolwa kya Melanota ku kusituka kisinziira ku bulungibwansi bw’olujegere lw’okusaasira olw’omugongo (lumbar paravertebral sympathetic chain). Okwawukana ku ekyo, Melanota eyafukibwa mu corpus cavernosum (1 μg) teyalaze mulimu gwonna gwa promoter. Okusala omugongo oba okusalako enjuyi zombi ez’obusimu bw’omu kifuba oba obusimu obw’omugongo obw’obusajja tekyakosa mirimu gya kutumbula Melanota eyingizibwa mu misuwa (1 mg/kg), ekyongera okulaga nti ekikolwa ekitumbula Melanota ku kusituka okusinga kiyita mu kkubo ly’obusimu obw’okusaasira okusinga obusimu bw’omu kifuba oba obusimu bw’omugongo obw’obusajja [6] ..
Okwongera ku nneeyisa y’abakyala mu kwegatta:
Okunoonyereza kuzudde nti Melanota naye alina ky’akola ku nneeyisa y’abakyala mu by’okwegatta. Mu nvunza enkazi, envunza ezaggyibwako enkwaso ezasooka okujjanjabwa n’eddagala lya estradiol benzoate (EB) ne progesterone (P), okukuba empiso ya Melanota mu misuwa (1 ne 3 mg/kg) kyayongera ku muwendo gw’okubuuka, okufubutuka, n’okuwuubaala amatu, ekiraga nti progesterone esobola okukwatagana ne Melanota okwongera ku nneeyisa y’enkazi ey’okucamuka mu by’okwegatta [7] ..
Enkola ya MTII ku tumorigenicity y’obutoffaali bwa melanoma.
Ensibuko:PubMed [1] .
Melanota kintu ekirina emirimu mingi n’endagiriro z’okunoonyereza. Wammanga bijja kwanjula okunoonyereza okulala okukwatagana ku Melanota .
Okuyingiza omuntu okusituka:
Mu kunoonyereza okumu, kyazuuliddwa nti ne Melanota alina ky’akola ku nkola y’okuzaala. Okugeza, Melanota asobola okuvaako obusajja okusituka mu ngeri etaali ya bulijjo. Abalwadde abamu baafuna okusituka okuluma oluvannyuma lw’okukuba empiso ya Melanota wansi w’olususu , era era ne balaga obubonero bw’okucamuka kw’obusimu obusaasira, gamba ng’omutima okweyongera, puleesa okulinnya, obutawummula, n’okutuuyana okuyitiridde [8] .Kino kiraga nti Melanota eyinza okukosa enkola y’omusaayi n’okulungamya obusimu bw’ebitundu by’okuzaala nga ekola ku bintu ebimu neurotransmitters ne receptor systems, bwe kityo ne kivaako enkyukakyuka mu nkola y’okusituka. Okugatta ku ekyo, mu kunoonyereza ku biwuka, ebintu bya melanocortin bisobola okuleeta enyimirira ya lordosis, ekitaputibwa ng’obujulizi obw’okwegatta okweyongera [8] , ekyongera okulaga nti enkosa ya Melanota ku nkola y’okuzaala eyinza okuba nga yeekuusa ku kucamuka mu kwegatta n’okulungamya enneeyisa y’okwegatta.
Okutumbula okukola melanin:
Nga synthetic melanocortin analogue, Melanota esobola okwesiba ku melanocortin I receptor (MC1R) okutumbula okukola melanin [9] .Ekisinga kituuka ku kino nga kitumbula okukula kwa melanocytes n’okulungamya emirimu gya tyrosinase. Ekikolwa kino eky’okutumbula okukola melanin kiwa Melanota omugaso oguyinza okukozesebwa mu kisaawe ky’olususu, okugeza, kiyinza okukola kinene mu kujjanjaba n’okuziyiza endwadde ezimu ez’olususu.
Okunoonyereza mu nsonga z’okulwanyisa ebizimba:
Mu kunoonyereza ku anti-tumor, okunoonyereza nga bakozesa enkola ya B16-F10 melanoma model kwazuula nti wadde nga Melanota terina kye yeekolera ku kweyongera kw’obutoffaali bwa melanoma, esobola bulungi okuziyiza okusenguka, okulumba, n’obusobozi bw’okukola colony mu butoffaali bwa melanoma. Okusiiga Melanota mu kitundu nakyo kisobola okukendeeza ennyo ku kukula kw’ekizimba mu mbeba ezirina obulwadde bwa melanoma obuteereddwawo. Enkola yaayo ey’okukola kwe kuleeta upregulation ya phosphatase ne tensin homolog (PTEN) okuyita mu melanocortin 1 receptor (MC1R), bwe kityo ne kiziyiza okukulaakulana kwa melanoma nga downregulating cyclooxygenase II (COX-2)/prostaglandin E2 (PGE2) signaling pathway [1]..
Enkola y’obujjanjabi ku bulwadde bwa autism:
Okunoonyereza okumu kwakozesa enkola ya maternal immune activation (MIA) mouse model of autism okwekenneenya obusobozi bw’obujjanjabi bw’ekirungo kya melanocortin receptor 4 agonist M Melanota ku mpisa eziringa autism mu mbeba ensajja enkuze [10] .Embeba ensajja eza MIA zalaga engeri eziringa autism, omuli okukosa ebiraga enneeyisa y’abantu, okukendeeza ku mpuliziganya y’amaloboozi, n’okweyongera mu nneeyisa y’okuddiŋŋana. Okugaba Melanota ku mbeba ensajja eza MIA okumala ennaku musanvu ez’omuddiring’anwa kyavaako okulongoosa mu bipimo by’enneeyisa y’abantu. Tewaaliwo nkyukakyuka nnene mu bipimo by'enneeyisa y'embeera z'abantu mu mbeba ensajja eza C57 ezirina embeera eya bulijjo oluvannyuma lw'okujjanjabwa ne Melanota . Okugatta ku ekyo, mu mbeba eza bulijjo eza C57, tewaaliwo nkyukakyuka mu nneeyisa eziringa okweraliikirira oba eziddiŋŋana oluvannyuma lw’okujjanjabwa ne Melanota , naye waaliwo okukendeera okw’amaanyi mu buzito bw’omubiri oluvannyuma lw’okujjanjabwa mu ngeri ya subacute. Ebiwandiiko bino biraga nti Melanota ddagala ddungi eriyinza okulongoosa obuzibu bw’enneeyisa eringa autism mu nkola ya autism ey’ebibe ebisajja ebikulu ebya MIA.
Okuzzaawo obuzibu mu kujjukira:
Okunoonyereza kulaga nti emmere erimu amasavu amangi (HF) kikakasibwa nti eyongera ku bulabe bw’okwonooneka kw’obusimu n’endwadde z’obusimu. Okunoonyereza kuno kwanoonyereza ku nkolagana esoboka wakati w’emmere, Melanota targeting melanocortin receptors, n’enneeyisa y’ebyennyanja ebiyitibwa zebrafish [11] . Ekyewuunyisa, n’emmere ya HF ey’ekiseera ekitono eyamala ebitundu nga 1% ku bulamu bw’ebyennyanja ebiyitibwa zebrafish yakosa nnyo enkulaakulana. Bw’ogeraageranya n’ebyennyanja ebiyitibwa zebrafish ebyaliisibwa emmere ey’okufuga, ebyennyanja ebiyitibwa zebrafish ebyaliisibwa emmere ya HF byalaga okulemererwa okujjukira, okweraliikirira okweyongera, n’okukendeeza ku mpisa y’okunoonyereza oluvannyuma lwa wiiki ssatu zokka. Era obutali buno buno obuva ku mmere ya HF bwakyusibwa Melanota . Ebisolo ebyaliisibwa emmere ya HF ne bijjanjabwa ne Melanota byalaga okujjukira okutegeera, okweraliikirira, n’enneeyisa y’okunoonyereza okufaananako n’ezo ez’ekibinja ekifuga. Okunoonyereza kuno kuwa obujulizi nti n’endya ya HF ey’ekiseera ekitono esobola okukosa okujjukira n’embeera y’omuntu, era kwe kunoonyereza okusoose okulaga nti Melanota asobola okuzzaawo enkyukakyuka zino.
Okulungamya enneeyisa mu bantu:
Mu kitundu ky’okunoonyereza ku busimu, kyazuulibwa nti Melanotan-II esobola okulung’amya enneeyisa y’abantu ng’esitula ebikwata ku melanocortin n’oluvannyuma n’ekola enkola ya oxytocin ey’omu makkati [12] . Okusingira ddala, oluvannyuma lw’okuweebwa Melanota mu nkola, okukuba empiso mu misuwa okusinga okuweebwa mu nnyindo kuyinza okuleeta ennyo okwolesebwa kwa Fos mu busimu obuyitibwa magnocellular neurons obwa supraoptic nucleus (SON) ne paraventricular nucleus (PVN) obwa hypothalamus, era okuddamu kuno kuyinza okukendeezebwa nga kuziyiza okujjanjabwa n’ekirungo kya melanocortin antagonist SHU-9119. Ebiwandiiko ebikwata ku masanyalaze byalaga nti okukuba empiso ya Melanota mu misuwa kuyinza okwongera ku mutindo gw’okukuba kw’obusimu bwa oxytocin mu SON. Kino kiraga nti Melanota erina ekikolwa eky’okulungamya ku nkola ya oxytocin ekwatagana n’enneeyisa y’embeera z’abantu mu nkola y’obusimu, era enkola yaayo ey’okukola eyinza okuba okulung’amya emirimu n’okufulumya obusimu bwa oxytocin nga ekola ku bikwata ebitongole n’amakubo agalaga obubonero.
Okunoonyereza ku mugejjo n’obulamu bw’enkyukakyuka mu mubiri:
Mu nsonga z’omugejjo n’obulamu bw’enkyukakyuka y’emmere, okunoonyereza okumu kwakozesa enkola y’obuzaale bw’ebibe ebibulamu pituitary adenylate cyclase-activating polypeptide (PACAP) era ne kuzuula nti eddagala erikwata melanocortin receptor agonist Melanota lisobola okutaasa ekitundu ku busobozi bw’ebbugumu obw’obuzibu obw’ebibe ebibulamu PACAP mu kiseera ky’okutuukagana n’embeera ennyogovu. Kino kiraga nti PACAP eyinza okukola omulimu waggulu w’enkola ya melanocortin, okulungamya emirimu gy’obusimu obw’okusaasira obw’ebitundu by’amasavu ebya kitaka mu mbeba, bwe kityo n’ekola ku mugejjo n’obulamu bw’enkyukakyuka y’emmere [13]..
Okulungamya enkyukakyuka mu mubiri n’ebbugumu ly’omubiri:
Melanota era erina kinene ky’ekola ku nkola y’endwadde z’omubiri. Okugeza, okuweebwa Melanota mu lubuto mu mbeba kiyinza okuleeta okukendeeza ku mubiri (profound and transient hypometabolism/hypothermia) [14] .Okunoonyereza kulaga nti mu mbeba ezitaliimu mast cells, hypothermia ereetebwa Melanota eggyibwawo, ekiraga nti okwetaba kw’obutoffaali obuyitibwa mast cells kwetaagibwa. Melanota ereeta hypothermia mu mbeba nga ekola mast cells n’okusitula histamine 1 receptor, era enkola yaayo ey’okukola erimu okukwatagana kw’ensonga eziwera endocrine n’ebikwata.
Mu kumaliriza, ng’ekintu ekikoleddwa mu ngeri ey’ekikugu ekisikiriza ennyo okufaayo, Melanota eraga engeri ez’enjawulo mu nnimiro eziwera. Mu kisaawe ky’olususu, nga yesiba ku bikwata ebitongole ku melanocytes, esobola bulungi okutumbula okukola kwa melanin, okuwa enkola etali ya kinnansi ey’okusiiga enviiri eri abo abaagala langi ennungi ey’ekikomo. Bw’ogeraageranya n’okulongoosa olususu ng’omala ebbanga eddene ng’olaba emisinde gya ultraviolet, Melanota esobola okwewala okwonooneka obutereevu kw’emisinde gya ultraviolet ku lususu n’okukendeeza ku bulabe obuyinza okuva mu kwokya omusana, okukaddiwa kw’olususu, n’okutuuka ku kookolo w’olususu.
Okusinziira ku ndowooza y’okulungamya enkola y’okwegatta, Melanota erina akakwate akalungi ku kusitula okusituka kw’obusajja mu ngeri eyeetongodde n’okutumbula okusikirizibwa kw’okwegatta. Kino kiyinza okugonjoola ensonga ennungi eri abantu abamu abalina obuzibu mu kwegatta oba abo abasuubira okulongoosa obumanyirivu bwabwe mu kwegatta. Kiyinza okutuuka ku kikolwa ekirungi ku nkola y’okwegatta nga kikola amakubo ag’enjawulo mu busimu obw’omu makkati n’ag’okumpi n’okulungamya ebikwatagana n’obusimu n’ebikwata, ne kiwa ebipya ebisoboka okutumbula obulamu bw’okwegatta.
Mu kunoonyereza ku mugejjo n’obulamu bw’enkyukakyuka mu mubiri, Melanota era alaga ebirungi ebiyinza okuvaamu. Kiyinza okusobola okutereeza enkyukakyuka y’amaanyi n’ebbugumu ly’omubiri era nga kirina ekikolwa ekimu eky’okulongoosa ku nkola y’amasavu okukosebwa mu mugejjo. Ewa obulagirizi obupya obw’okunoonyereza ku bujjanjabi bw’omugejjo n’okuddukanya obulamu bw’enkyukakyuka mu mubiri, ekiyamba mu kukola enkola empya ez’obujjanjabi n’okutumbula embeera y’obulamu bw’abalwadde abagejjulukuka.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Cousen, P munoonyereza ng’essira asinga kulissa mu mulimu gwa Dermatology Allergy. Omulimu gwe mu kitundu kino gubadde gukwatagana n’ebibiina ebiwerako, omuli South Tees Hosp NHS Fdn Trust, James Cook University Hospital, Royal Cornwall Hospital, University of Sheffield, ne Chesterfield Royal Hosp. Okusukka okukuguka kwe okukulu mu Dermatology Allergy, Cousen, P by’ayagala okunoonyereza n’emirimu gy’akola biyinza okutuuka ku bitundu ebikwatagana nga immunology, okusinziira ku kakwate akazaaliranwa wakati w’allergy n’abaserikale b’omubiri. Kino kiyinza okuzingiramu okunoonyereza ku ngeri abaserikale b’omubiri gye baddamu okuvaako embeera z’olususu ezirina alergy n’okunoonyereza ku nkola empya ez’obujjanjabi okukyusakyusa mu ngeri zino.
Okugatta ku ekyo, okunoonyereza kwe kuyinza okuzingiramu okugezesa obujjanjabi obupya obw’ensusu, okunoonyereza ku nkola y’ebiziyiza olususu n’omulimu gwayo mu kuziyiza alergy, n’okunoonyereza ku nsonga z’obuzaale ezireetera abantu ssekinnoomu okufuna alergy y’olususu. Ekirala. Cousen, P ewandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [4].
