1kits (Ebipipa 10) .
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▎ GHK-cu kye ki?
GHK-cu kizibu ekikolebwa okusiba kwa tripeptide —ekoleddwa glycine (Gly), histidine (His), ne lysine (Lys) eziyungiddwa ku peptide bonds —ku divalent copper ions (Cu⊃2;+). Mu nsengekera yaayo ey’eddagala, empeta ya imidazole ey’ekisigadde kya histidine ekola ekiyungo ekinywevu eky’okukwatagana ne ion y’ekikomo, ne kikola ekirungo ekikwatagana n’ensengekera y’ekifo eyeetongodde n’emirimu gy’ebiramu.
▎ GHK - Enzimba ya Cu
Ensibuko: PubChem |
Omutendera: Gly-His-Lys Ensengekera ya molekyu: C 28H 46CuN 12O8 Obuzito bwa molekyu: 742.3g/mol Ennamba ya CAS: 130120-56-8 PubChem CID: 9831891. Omuntu w’abantu Ebifaanagana: Ekikomo kya Bisprezatide;DL1TR6W6VM |
▎ GHK - Okunoonyereza ku Cu
Ensibuko y’okunoonyereza eya GHK-cu eri etya?
Mu myaka gya 1970, bannassaayansi b’Amerika abaali banoonyereza ku ngeri omusaayi gw’omuntu gye gukwata ku bitundu by’omubiri okuva mu bibinja by’emyaka egy’enjawulo baakola okwetegereza okw’amaanyi. Plasma okuva mu bavubuka bwe yagattibwa mu bitundu by’ekibumba okuva mu bantu abakadde, ebitundu by’ekibumba ebikaddiye byatandika okukola obulungi obutoffaali obw’enjawulo ng’obw’ebitundu ebito. Oluvannyuma lw’okwekenneenya mu bujjuvu, mu 1973, yasobola bulungi okwawula GHK-Cu okuva mu serum y’omuntu. Ekizibu kino kikolebwa ekirungo kya tripeptide ekikolebwa glycine, histidine, ne lysine nga bisibiddwa bulungi ku ion y’ekikomo. Okunoonyereza okulala kwalaga nti GHK-Cu mu butonde eriwo mu nkola z’omubiri gw’omuntu munda mu ntuuyo, omusaayi, n’omusulo. Emiwendo gyayo egy’obungi gikwatagana nnyo n’emyaka: gituuka ku 200ng/mL mu plasma y’abaana ab’emyaka 20, naye nga gikendeera nnyo okutuuka ku 80ng/mL ku myaka 60.
Okunoonyereza okuddirira kukyagenda mu maaso n’okugaziya ensalo z’okutegeera kwa GHK-Cu. Ku ntandikwa y’emyaka gya 1980, abamanyi baazuula nti omubiri gw’omuntu gufulumya GHK mu bifo ebifunye obuvune, nga bateebereza n’obuvumu omulimu gwayo oguyinza okukolebwa ng’akabonero akakulu akasooka okuddaabiriza olususu. Okuva olwo, okunoonyereza okunene kwesigamye ku kifo kya GHK-Cu mu kuddaabiriza ebitundu by’omubiri naddala mu kuzzaawo olususu. GHK-Cu esitula okukola kwa kolagini, elastin, ne glycosaminoglycans ate nga etereeza emirimu gya metalloproteinases n’ebiziyiza zo. Kikola ebirungi mu kuziyiza okuzimba, okuziyiza obuwuka obuleeta obuwuka obuleeta obulwadde, n’okukola emisuwa, mpolampola ne kifuuka ekintu eky’okunoonyereza mu bintu ebingi omuli biochemistry, dermatology, n’eddagala erizza obuggya.
Enkola ki ey’okukola ku GHK-Cu?
Okutumbula Okuwona Ebiwundu
Okukula n’okusenguka kw’obutoffaali: GHK-Cu esitula okukula n’okusenguka kw’obutoffaali obw’enjawulo, omuli fibroblasts z’olususu n’obutoffaali bw’omubiri. Okugeza, mu bifo ebiwundu by’olususu, kyanguya okusengejja ebitundu by’omubiri eby’ebweru w’obutoffaali nga kolagini ne elastin nga bikolebwa fibroblasts, ne kiwa obuwagizi bw’enzimba y’okuwona kw’ebiwundu. Mu kiseera kye kimu, kisikiriza obutoffaali bw’omubiri (endothelial cells) okusenguka okugenda mu kiwundu, ne kitumbula okutondebwa kw’emisuwa emipya. Kino kituusa ebiriisa ebingi ne omukka gwa oxygen mu kiwundu, ne kyanguyira okuwona [1] ..
Okulungamya ensonga z’okukula: Ekizibu kino kikyusakyusa okwolesebwa n’okufulumya ensonga z’okukula eziwera, gamba nga transforming growth factor-β (TGF-β) ne vascular endothelial growth factor (VEGF). Nga tutwala VEGF ng’ekyokulabirako, GHK-Cu etumbula okufulumya kwayo, nga kino nakyo kisitula okukula kw’obutoffaali bw’emisuwa n’okutondebwa kw’emisuwa —enkola enkulu mu kuwona kw’ebiwundu [1]..
Ebikolwa Ebiziyiza okuzimba
Okuziyiza Abatabaganya Abazimba: GHK-Cu enyigiriza okukola n’okufulumya ebitabaganya ebizimba ebingi, omuli tumor necrosis factor-α (TNF-α) ne interleukin-1β (IL-1β). Abatabaganya bano bakola emirimu emikulu mu kuddamu kw’okuzimba. Nga eziyiza okwolesebwa kwazo, GHK-Cu ekendeeza ku maanyi n’obudde bw’okuzimba, bwe kityo ne kikendeeza ku kwonooneka kw’ebitundu [2]..
Okukyusakyusa obutoffaali bw’abaserikale b’omubiri: Era kitereeza enkola y’obutoffaali bw’abaserikale b’omubiri. Nga ekyusakyusa macrophage polarization eri anti-inflammatory macrophages, kikendeeza ku kufulumizibwa kw’abatabaganya okuzimba era kitumbula okuddaabiriza ebitundu [2] ..
Okuddaabiriza DNA
Okukola amakubo g’okuddaabiriza: GHK-Cu ekola amakubo g’okuddaabiriza DNA mu butoffaali. Obutoffaali bwe bwonoonebwa ensonga ez’enjawulo ez’omunda oba ez’ebweru, butandika enkola eziddiriŋŋana ez’okuddaabiriza DNA. GHK-Cu etumbula okuddaabiriza DNA eyonoonese nga etereeza emirimu gy’enziyiza ezikwatagana, nga DNA polymerase ne ligase, bwe kityo ne kikuuma obutebenkevu bw’ensengekera y’obutonde [2]..
Obukuumi bw’ebirungo ebiziyiza obuwuka obuleeta obulwadde: Kirina obusobozi bw’okuziyiza obuwuka obuleeta obulwadde, ekikendeeza ku kwonooneka kwa DNA okuleetebwa ebika bya oxygen ebikola (ROS). ROS esobola okuleeta okukutuka kw’emiguwa gya DNA n’okufuuka base oxidation. Nga esengejja ROS, GHK-Cu mu ngeri etali butereevu ekuuma DNA obutakwonooneka, n’ekola embeera ennungi ey’okuddaabiriza DNA [1]..
Okulungamya Enkyukakyuka y’Obutoffaali
Okutumbula Enkyukakyuka y’Amaaso: Ku bikwata ku nkyukakyuka y’amasoboza g’obutoffaali, GHK-Cu eyinza okukwata ku nkola ya mitochondria. Mitochondria zikola nga amaanyi g’obutoffaali, era GHK-Cu eyinza okutumbula obulungi bw’okukola amaanyi g’obutoffaali ng’etereeza emirimu gy’enziyiza ezikwatagana ne mitochondria —nga ezo ezikwatibwako mu nsengekera ya tricarboxylic acid ne oxidative phosphorylation —bwe kityo ne kituukiriza obwetaavu bw’amasoboza mu nkola z’obutoffaali ng’okukula n’okuddaabiriza [2]..
Okulungamya Okusengejja Ebintu: GHK-Cu era ekyusakyusa okusengejja ebintu ebikulu ebiri mu butoffaali. Nga bwe kyayogeddwako emabegako, kitumbula okusengejja ebitundu bya matrix eby’ebweru w’obutoffaali nga kolagini ne elastin. Okugatta ku ekyo, kikwata ku kusengejja n’okukyusakyusa ebintu ebiri mu butoffaali nga puloteyina n’amasavu, bwe kityo ne kikuuma emirimu gy’omubiri egy’obutoffaali egya bulijjo [2]..
Enkozesa ya GHK-Cu ze ziruwa?
Okuwona ebiwundu: GHK-Cu erina obusobozi okutumbula okuwona ebiwundu. Kisitula okuzimba emisuwa, ne kiwa ebiriisa ebingi ne omukka gwa oxygen mu kifo ekiwundu, bwe kityo ne kyanguya okuddaabiriza n’okuddamu okukola ebitundu by’omubiri. GHK-Cu era ewagira omulimu gwa fibroblasts z’olususu, okutumbula okusengejja kwa kolagini, elastin, ne glycosaminoglycans. Kino kiyamba mu kuzimba ekitundu ekiramu eky’ebweru w’obutoffaali era kyanguya enkola y’okuwona kw’ebiwundu. Mu kunoonyereza kwa Pickart L ku buvune bw’olususu, okujjanjaba n’eddagala eririmu GHK-Cu kyanguya nnyo sipiidi y’okuwona kw’ebiwundu n’okulongoosa omutindo gw’okuwona [2]..
Ebikosa okuzimba: Kikendeeza ku kuddamu kw’okuzimba nga kiziyiza amakubo g’obubonero agakwatagana n’okuzimba. Mu byombi lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model n’okugezesa mu vitro ne RAW 264.7 macrophages, obujjanjabi bwa GHK-Cu bwakendeeza ku kukola ebika bya oxygen ebikola (ROS), okwongera ku mirimu gya superoxide dismutase (SOD), era ne bukendeeza ku kuzaala ebizimba ebizimba nga necrosis factor -α (TNF-α) ne interleukin-6 (IL-6), etuukibwako nga eziyiza amakubo g’obubonero bwa NF-κB p65 ne p38 MAPK. Bwe kityo, GHK-Cu eraga obusobozi bw’okujjanjaba endwadde ezeekuusa ku kuzimba nga ALI/Acute Respiratory Distress Syndrome (ARDS) [3]..
Obukuumi bw’obutoffaali: Bulaga ebikolwa ebiwerako eby’okukuuma obutoffaali. Mu bulwadde bw’amawuggwe obutawona (COPD), bukuuma n’okuddaabiriza ebitundu by’amawuggwe ate nga buzzaawo enkola ya COPD fibroblast. Era kiziyiza molekyu nga NFκB, eziteeberezebwa okwanguya endwadde z’okukaddiwa, nga ziraga obusobozi bw’okulwanyisa okukaddiwa. Okugatta ku ekyo, eraga emirimu gy’okulwanyisa okweraliikirira, okukendeeza obulumi, n’okulwanyisa obulumbaganyi, era ekola emirimu gy’okuyonja obutoffaali ng’eyita mu nkola ya proteasome, n’ewa obukuumi obw’enjawulo obw’obutoffaali [2]. .
Okuddaabiriza DNA: GHK-Cu yeetaba mu nkola z’okuddaabiriza DNA mu butoffaali, eyamba okukuuma obutebenkevu bw’ensengekera y’obutonde (genomic stability) n’okukendeeza ku bulwadde bw’obutoffaali n’ensonga z’okukaddiwa ezireetebwa okwonooneka kwa DNA okukuŋŋaanyiziddwa. Kino kiwagira okuziyiza n’okujjanjaba endwadde ezeekuusa ku kwonooneka kwa DNA [2] ..
Mu bufunzi
Nga endogenous tripeptide-copper complex, GHK-Cu eraga emirimu gy’ebiramu egy’ebitundu bingi. Nga ekola amakubo agalaga obubonero nga PI3K/Akt ne MAPK/ERK, kitumbula okukula kw’obusimu obuyitibwa fibroblast, angiogenesis, n’okukola extracellular matrix synthesis, nga kikola kinene nnyo mu kuwona ebiwundu. Era eraga emirimu gy’okulwanyisa okuzimba, okuziyiza obuwuka obuleeta obulwadde, n’okukyusa obusimu obuziyiza endwadde, okukendeeza ku kwonooneka kw’okuzimba ebitundu by’omubiri n’okuyamba mu kuddaabiriza obuvune n’okuyingira mu nsonga z’endwadde ezizimba.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Loren Pickart yali mukugu mu by’obutonde omututumufu era omutandisi wa Skin Biology Inc., ng’akuguse mu kunoonyereza ku peptides z’ekikomo n’okuzikozesa mu bulamu bw’olususu n’okukaddiwa. Yazuula ekirungo ekiyitibwa copper peptide GHK-Cu mu 1973 bwe yali mu kunoonyereza kwe okw’obusawo mu yunivasite y’e California, San Francisco. Okuzuula kuno kwavaako okukola peptides z’ekikomo ezizza obuggya olususu n’okutandikawo kkampuni ya Skin Biology Inc. mu 1994. Omulimu gwe guyamba nnyo mu kutegeera ebiramu by’olususu n’okukola eddagala eriweweeza ku kukaddiwa. Okunoonyereza kwa Pickart kukyagenda mu maaso n’okukwata ku by’obujjanjabi bw’ensusu n’obusawo obuzza obuggya. Loren Pickart awandiikiddwa mu kiwandiiko ekijuliziddwa [2].
▎ Ebiwandiiko Ebikwatagana
[1] Sun L, Li A, Hu Y, Li Y, Shang L, Zhang L. Okwekuŋŋaanya Fluorescent ne Antibacterial GHK‐Cu Nanoparticles okukozesebwa okuwonya ebiwundu. Enkola z’obutundutundu n’obutundutundu 2019; 36: 1800420.DOI: 10.1002/ppsc.201800420. Enkola y’okukuuma obutonde bw’ensi.
[2] Pickart L, Margolina A. Ebikolwa eby’okuzza obuggya n’okukuuma ebya GHK-Cu Peptide mu kitangaala ky’ebiwandiiko by’obuzaale obupya. Ekitabo ky’ensi yonna ekya Sayansi wa Molekyulu 2018; 19. https://api.semanticscholar.org/CorpusID:51609461. Enkola y’okukuuma obutonde bw’ensi.
[3] Park JR, Lee H, Kim S. I., Yang S. R., ne bannaabwe abalala. Tri-peptide GHK-Cu complex etereeza obuvune obw’amawuggwe obuva ku lipopolysaccharide mu mbeba. Oncotarget 2016 mu ssaza ly’e Mulago; 7 (36): 58405-58417.DOI: 10.18632 / ku kiruubirirwa.11168.
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 kwokka mu kisenge (in vitro research). Okunoonyereza mu kisenge (in vitro research) (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.