Bya Cocer Peptides 
omwezi gumu emabega
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.
Okwanjula
TB 500 (Thymosin Beta-4 Fragment 17–23) kitundu kya bioactive ekikwatagana ennyo n’enkola enkulu eziwera mu physiology y’omuntu naddala mu kuddaabiriza ebitundu by’omubiri n’okutambula kw’obutoffaali.
Ekifaananyi 1 Ensengekera y’eddagala ly’ekitundu kya TB 500 (17–23).
Ebikulu ebikwata ku TB 500 Fragment (17–23) .
Ekitundu kya TB 500 (17–23) kye kitundu kya N-terminal acetylated 17–23 ekya thymosin beta-4 y’omuntu (Thymosin Beta-4). N-terminal acetylation ekola kinene nnyo mu kulungamya enkolagana ya puloteyina ne puloteyina n’okubeera mu kifo mu butoffaali. Okubeerawo kw’ebibinja bya aseeti kuyinza okukyusa ensaasaanya ya kisannyalazo kya molekyu n’ensengekera y’ekifo, bwe kityo ne kikwata ku busobozi bwayo okusiba ne biomolekyulu endala. Mu mubiri gw’omuntu, thymosin β4 ye peptide esaasaanidde nnyo, era TB 500 Fragment (17–23), ng’ekitundu kyayo ekitongole, esobola okukolebwa okuyita mu nkola za endogenous proteolytic.
Enkola y’okukola kw’ekitundu kya TB 500 (17–23) .
(1) Okusenguka kw’obutoffaali ne Chemotaxis
Ebikosa Obutoffaali bw’Endothelial: TB 500 Fragment (17–23) etumbula okusenguka kw’obutoffaali bw’omubiri, enkola enkulu mu kukola emisuwa. Mu kiseera ky’okuwona ebiwundu oba okuddaabiriza ebitundu, obutoffaali bw’omubiri (endothelial cells) bulina okusenguka ne bugenda mu bifo ebyonooneddwa okukola emikutu gy’emisuwa emipya, okugabira omukka gwa oxygen n’ebiriisa mu bitundu by’omubiri. TB 500 Fragment (17–23) esobola okutumbula okutambula kw’obutoffaali bw’omubiri (endothelial cell migration) nga ekola omuddirirwa gw’amakubo agalaga obubonero mu butoffaali, gamba nga ekkubo ly’obubonero erya PI3K-Akt, erifuga okuddamu okutegeka obutoffaali bw’obutoffaali. Okukola kw’ekkubo ly’obubonero bwa PI3K-Akt kitumbula okukola polimeeri n’okuggya polimeeri ya actin, okusobozesa obutoffaali okugaziya pseudopodia n’okugenda mu maaso.
Chemotactic effect ku butoffaali bw’abaserikale b’omubiri: Akatundu kano era kalaga chemotactic effects ku butoffaali bw’abaserikale b’omubiri, ne kasikiriza macrophages, neutrophils, n’obutoffaali obulala obw’abaserikale mu bifo ebizimba oba obuvune. Macrophages zikola kinene mu kuddaabiriza ebitundu, kubanga zisobola okugogola ebitundu ebyonooneddwa n’obuwuka obuleeta endwadde ate nga zifulumya ensonga ez’enjawulo ez’okukula ne cytokines okutumbula okuddaabiriza ebitundu by’omubiri n’okuddamu okukola. Ekitundu kya TB 500 (17–23) kyesiba ku bikwata ebitongole ku ngulu w’obutoffaali obuziyiza endwadde, ne kikola amakubo g’obubonero mu butoffaali okulungamya obutoffaali bw’abaserikale okutuuka mu kifo we bufunye obuvune.
(2) Okuddaabiriza n’okuzza obuggya ebitundu by’omubiri
Okutumbula okukula kw’obutoffaali obuyitibwa fibroblast n’okusengejja kolagini: Fibroblasts kye kika ky’obutoffaali obusookerwako mu bitundu ebiyunga era zivunaanyizibwa ku kusengejja n’okufulumya ebitundu by’omubiri eby’ebweru w’obutoffaali nga kolagini mu kiseera ky’okuwona ebiwundu. TB 500 Fragment (17–23) esobola okusitula okukula kw’obutoffaali obuyitibwa fibroblast, okwongera ku muwendo gw’obutoffaali era bwe kityo ne kyanguya okukola kolagini. Ekitundu kino kisobola okulinnyisa okwolesebwa kw’obuzaale obukwatagana n’okusengejja kolagini, nga COL1A1 ne COL3A1, ate nga kitumbula enkyukakyuka ya kolagini oluvannyuma lw’okuvvuunula munda mu fibroblasts, bwe kityo ne kilongoosa omutindo gwa kolagini n’okutebenkera. Ebikolwa bino biyamba mu kutondebwawo kw’ekisenge ekinywevu eky’ebweru w’obutoffaali, ekitumbula okuwona kw’ebiwundu n’okuddaabiriza ebitundu by’omubiri.
Okuddaabiriza ebitundu by’ebinywa: Mu kuddaabiriza obuvune bw’ebinywa, TB 500 Fragment (17–23) nayo ekola kinene. Kitumbula okukola n’okukula kw’obutoffaali bwa setilayiti, nga buno butoffaali bwa myogenic stem cells mu binywa by’amagumba nga bulina obusobozi okwezza obuggya n’okwawukana mu fibers z’ebinywa. TB 500 Fragment (17–23) etereeza ekkubo ly’obubonero bwa MyoD-Myogenin munda mu butoffaali bwa setilayiti, n’etumbula okwawukana kwabwo mu myotubes, oluvannyuma ne zigatta okukola ebiwuzi by’ebinywa ebipya, bwe kityo ne kituuka ku kuddaabiriza n’okuddamu okukola ebitundu by’ebinywa. Akatundu kano era kasobola okukendeeza ku kuddamu kw’okuzimba oluvannyuma lw’okulumwa ebinywa, okukendeeza ku kwonooneka okulala ku bitundu by’ebinywa ebiva ku kuzimba.
(3) Ebikolwa ebiziyiza okuzimba
Okuziyiza okwolesebwa kw’ensonga ezizimba: TB 500 Fragment (17–23) esobola okuziyiza okwolesebwa kw’ensonga ez’enjawulo ezizimba, omuli tumor necrosis factor-α (TNF-α) ne interleukin-1β (IL-1β). Ensonga zino ezizimba zikola kinene mu kuddamu kw’okuzimba, era okulaga kwazo okuyitiridde kuyinza okuvaako okugaziwa n’okusigala kw’okuzimba, ne kivaako ebitundu by’omubiri okwonooneka. TB 500 Fragment (17–23) esobola okukendeeza ku kuwandiikibwa n’okuvvuunula ensonga ezizimba nga eziyiza okukola kw’ekkubo ly’obubonero bwa nuclear factor-κB (NF-κB), bwe kityo ne kikendeeza ku kuddamu kw’okuzimba. NF-κB nsonga nkulu ey’okuwandiika ku musingi gw’okukyusa obubonero bw’okuzimba, era okukola kwayo kuyinza okutumbula okwolesebwa kw’obuzaale obuwera obukwatagana n’okuzimba.
Okulungamya okuddamu kw’okuzimba kw’obutoffaali bw’abaserikale: Ng’oggyeeko okuziyiza okwolesebwa kw’ensonga ezizimba, TB 500 Fragment (17–23) era esobola okulungamya okuddamu kw’okuzimba kw’obutoffaali bw’abaserikale. Kiyinza okuziyiza okuwunyiriza kwa macrophages okudda ku kika kya pro-inflammatory (ekika kya M1) n’okutumbula polarization yazo eri ekika ekiziyiza okuzimba (ekika kya M2). Macrophages ez’ekika kya M1 okusinga zifulumya ensonga eziyamba okuzimba, nga zeetaba mu kutandika n’okugaziya okuzimba; so nga macrophages ez’ekika kya M2 zifulumya ebintu ebiziyiza okuzimba, ebitumbula okuddaabiriza ebitundu by’omubiri n’okulungamya abaserikale b’omubiri. TB 500 Fragment (17–23) etereeza embeera ya polarization ya macrophages, okulungamya okuddamu kw’okuzimba eri obulagirizi obulungi okuddaabiriza ebitundu.
Okukozesa ekitundu kya TB 500 (17–23) mu nnimiro y’obusawo
(1) Okuwona Ebiwundu
Ebiwundu by’olususu: Mu kuwona ebiwundu by’olususu, TB 500 Fragment (17–23) eraga ebikolwa eby’amaanyi eby’okutumbula. Okunoonyereza nga tekunnabaawo kulaga nti okusiiga eddagala eririmu TB 500 Fragment (17–23) ku mubiri kyanguya okuggalawo ebiwundu n’okulongoosa omutindo gw’okuwona. Kino okusinga kiva ku nkola yaayo ey’okulungamya ey’enjawulo ku butoffaali bw’omubiri (endothelial cells), fibroblasts, n’obutoffaali bw’abaserikale b’omubiri. Okutambula kw’obutoffaali bw’omubiri mu bwangu kutumbula okutondebwa kw’emisuwa emipya, ne kiwa ekiwundu ekiriisa ekimala; okweyongera kw’obusimu obuyitibwa fibroblast n’okusengejja kolagini kivaamu ebitundu ebiyunga ebinywevu ennyo mu kifo ekiwundu; era ebikolwa by’obutoffaali bw’abaserikale b’omubiri (chemotactic and anti-inflammatory effects) bikendeeza ku buzibu obuziyiza obw’okuddamu kw’okuzimba ku kuwona kw’ebiwundu. Mu kujjanjaba ebiwundu ebimu ebitawona, gamba ng’amabwa g’ebigere aga ssukaali, TB 500 Fragment (17–23) nayo eraga omugaso oguyinza okujjanjaba. Abalwadde ba ssukaali balwawo okuwona ebiwundu n’obulabe bw’okukwatibwa obulwadde obweyongera olw’obungi bwa sukaali mu musaayi. TB 500 Fragment (17–23) esobola okulongoosa microenvironment y’ekitundu, okutumbula okutambula kw’obutoffaali n’okukula, n’okutumbula emikisa gy’okuwona mu biwundu ebitawona.
Ebiwundu by’ebitundu eby’omunda: Ku biwundu by’ebitundu eby’omunda, gamba ng’amabwa mu lubuto n’okwonooneka kw’ekibumba, TB 500 Fragment (17–23) nayo erina ebiyinza okujjanjaba. Mu nkola y’amabwa g’omu lubuto, okugaba TB 500 Fragment (17–23) kitumbula okukula n’okuddaabiriza obutoffaali bw’omubiri mu kifo ky’amabwa, ekikendeeza ku kitundu ky’amabwa. Enkola yaayo ey’okukola ekwatagana n’okutumbula okutambula kw’obutoffaali, okulungamya eby’okuddamu by’okuzimba, n’okwongera ku kusengejja kwa matrix ez’ebweru w’obutoffaali. Mu nkola y’obuvune bw’ekibumba, TB 500 Fragment (17–23) esobola okutumbula okuddamu okuzimba obutoffaali bw’ekibumba, okukendeeza ku kwonooneka kw’okuzimba ku bitundu by’ekibumba, n’okulongoosa ebiraga enkola y’ekibumba.
(2) Obujjanjabi bw’endwadde z’ebinywa n’amagumba
Okunyigirizibwa n’obuvune mu binywa: Mu ddagala ly’ebyemizannyo, okunyigirizibwa kw’ebinywa n’obuvune nsonga za bulijjo. TB 500 Fragment (17–23), olw’ebikolwa byayo eby’okuddaabiriza ku bitundu by’ebinywa, evuddeyo ng’ekiyinza okujjanjaba obuvune bw’ebinywa. Okugaba TB 500 Fragment (17–23) oluvannyuma lw’okunyigirizibwa kw’ebinywa kiyinza okwanguya okuddamu kw’amaanyi g’ebinywa n’okukendeeza ku kubeerawo kw’okuzimba ebinywa. Obulwadde bw’ebinywa kizibu ekitera okubaawo oluvannyuma lw’okulumwa ebinywa, ekivaako okukaluba kw’ebitundu by’ebinywa, okukendeeza ku bugumu, n’okukosa emirimu gy’ebinywa. TB 500 Fragment (17–23) etumbula okukola n’okusaasaana kw’obutoffaali bwa satellite, eziyiza okuddamu kw’okuzimba, era ekendeeza ku kutondebwa kw’obuwuzi bw’ebinywa, bwe kityo n’eyongera okuddaabiriza obuvune bw’ebinywa.
Obulwadde bw’amagumba: Obulwadde bw’amagumba bulwadde bwa nnyondo obutera okuvunda nga bumanyiddwa olw’okwonooneka kw’amagumba, okuzimba emisuwa n’okukula kw’amagumba. TB 500 Fragment (17–23) nayo eraga obusobozi mu kujjanjaba obulwadde bw’amagumba. Kiyinza okutumbula okukula n’okusengejja matrix ya chondrocytes, okuziyiza chondrocyte apoptosis, bwe kityo ne kikendeeza ku kuvunda kw’amagumba. Ebikolwa eby’okulwanyisa okuzimba ebya TB 500 Fragment (17–23) bisobola okukendeeza ku kuzimba kw’emisuwa, okumalawo obulumi bw’ennyondo, n’okukendeeza ku kuzimba. Okunoonyereza ku bisolo kulaga nti okukuba empiso ya TB 500 Fragment (17–23) mu bitundu by’omubiri (intra-articular injection) esobola okulongoosa enkola y’ennyondo mu bisolo eby’ekyokulabirako eby’obulwadde bw’amagumba n’okukendeeza ku kwonooneka kw’amagumba.
(3) Okujjanjaba endwadde z’emisuwa n’emisuwa
Myocardial infarction: Myocardial infarction bulwadde bwa maanyi obw’emisuwa n’emisuwa obuva ku myocardial ischemia ne necrosis olw’okuzibikira kw’emisuwa gy’omutima. TB 500 Fragment (17–23) erina omugaso oguyinza okukozesebwa mu kujjanjaba okuzimba emisuwa gy’omutima. Oluvannyuma lw’okusannyalala kw’omusuwa gw’omutima, ebitundu by’omutima biyita mu kuddamu okuzimba n’okufa kw’obutoffaali, ekivaako okukola kw’omutima okukosebwa. TB 500 Fragment (17–23) esobola okulongoosa enkola y’omutima oluvannyuma lw’okuzimba emisuwa gy’omutima ng’eziyiza okuddamu kw’okuzimba, okukendeeza ku kufa kw’obutoffaali bw’omutima, n’okutumbula okutondebwa kw’emisuwa. Okunoonyereza kulaga nti mu bikolwa by’ebisolo eby’okusannyalala kw’omutima, okukozesa TB 500 Fragment (17–23) kuyinza okukendeeza ku sayizi y’okusannyalala, okulongoosa ekitundu ky’okufulumya omutima, n’okutumbula emirimu gy’okukonziba n’okuwummulamu kw’omutima.
Okuddaabiriza obuvune bw’emisuwa: Mu mbeera z’obuvune bw’emisuwa, gamba ng’okwonooneka kw’endothelial oluvannyuma lw’okuyingira mu nsonga z’emisuwa, TB 500 Fragment (17–23) esobola okutumbula okutambula kw’obutoffaali bw’omubiri n’okukula, okwanguya okuddaabiriza endothelial, n’okukendeeza ku bulabe bw’okutondebwawo kw’obutoffaali obuyitibwa thrombus. Oluvannyuma lw’obuvune bw’emisuwa, kolagini abikkuddwa wansi w’endothelium esobola okuleetawo okunywerera kw’obutoffaali obuyitibwa platelet n’okukuŋŋaanyizibwa, ekivaako okutondebwa kw’obutoffaali obuyitibwa thrombus. TB 500 Fragment (17–23) etumbula okuddaabiriza obutoffaali bw’omubiri, okuzzaawo obulungi bw’obutoffaali bw’emisuwa, bwe kityo ne kikendeeza ku kutondebwa kw’omusaayi (thrombus formation) n’okukuuma enkola y’emisuwa eya bulijjo.
Mu bufunzi
TB 500 Fragment (17–23), nga peptide fragment erimu emirimu egy’enjawulo egy’ebiramu, eraga obulungi mu kuddaabiriza ebitundu by’omubiri, okusenguka kw’obutoffaali, n’ebitundu ebirala.
Ensonda
[1] Esposito S, Deventer K, Goeman J, n’abalala. Okusengejja n’okulaga obubonero bw’ekitundu kya N-terminal acetylated 17-23 ekya thymosin beta 4 ekyazuulibwa mu TB-500, ekintu ekiteeberezebwa okuba n’obusobozi bw’okukozesa doping[J]. Okukebera n'okwekenneenya eddagala, 2012,4 (9): 733-738.DOI: 10.1002 / dta.1402.
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