▎ Okunoonyereza ku livagen
Livagen okunoonyereza kuliko ki?
Endowooza ya Free Radical Theory of Aging: Mu myaka gya 1950, Harman yaleeta endowooza ya free radical theory of aging, ng’alaga nti free radicals ezikolebwa mu kiseera ky’okukyusakyusa obutoffaali zandilumba biomolecules, ekivaako obutoffaali okwonooneka n’okukaddiwa. Endowooza eno yawa omusingi gw’enzikiriziganya mu kunoonyereza ku bintu ebiziyiza okukaddiwa era n’ewaliriza bannassaayansi okunoonya ebintu ebiyinza okusaanyawo ebirungo ebiyitibwa free radicals oba okutumbula obusobozi bw’obutoffaali obuziyiza obuwuka obuleeta obulwadde.
Okuzuula Ebintu Ebiyitibwa Peptide: Olw’okunoonyereza okw’obwegendereza okugenda mu maaso ku biology, bannassaayansi bakizudde nti ebintu ebiyitibwa peptide bikola kinene mu bubonero bw’obutoffaali, okulung’amya enkyukakyuka mu mubiri, n’ebintu ebirala. Ebintu ebimu ebya peptide birina emirimu nga antioxidant, anti-inflammatory, n’okutumbula okuddaabiriza obutoffaali, ekiwa obulagirizi obupya eri okukola eddagala eppya eriziyiza okukaddiwa.
Okunoonyereza n’okukulaakulanya Livagen: Ku nsonga eno, bannassaayansi b’e Russia baakola Livagen nga basinziira ku kunoonyereza kwabwe ku bintu ebiyitibwa peptide. Baggya ebitundu bya peptide ebikola obulamu okuva mu bitundu by’ebisolo era okukkakkana nga bafunye Livagen oluvannyuma lw’okukeberebwa n’okulongoosa. Okunoonyereza kulaga nti Livagen esobola okulungamya enkola y’okukyusakyusa emmere y’obutoffaali n’okutumbula obusobozi bw’obutoffaali obuziyiza obuwuka obuleeta obulwadde, bwe kityo n’elwawo okukaddiwa kw’obutoffaali.
Enkola ya Livagen ekola ki?
1. Ebikosa Enkola y’okugaaya emmere
Okulungamya Enkola y’enziyiza z’okugaaya: Okunoonyereza kulaga nti Livagen (Lys-Glu-Asp-Ala) ye peptide enafuwa okusaanuuka mu mazzi. Peptide hydrolases mu kyenda ekitono teziyinza kuziyiza Livagen hydrolyze ku kigero ekitono ennyo [1] . Mu mbeera za in vitro, Livagen esobola okukendeeza ku mirimu gya glycyl-L-leucine dipeptidase mu kyenda ekitono ebitundu 50%. Oluvannyuma lw’okugabira envunza Livagen mu kamwa okumala wiiki bbiri, emirimu gy’enziyiza y’okugaaya emmere mu bisolo ebito gyakendeera, ate mu bisolo ebikadde ne gyeyongera. Kinajjukirwa nti mu mbeera ezisinga, enkola y’enziyiza y’envunza enkadde oluvannyuma lw’okufuna Livagen yali kumpi n’omutindo gw’ebisolo ebito mu kibinja ekifuga [1]..
2. Ebikosa Enkephalin Degrading Enzymes mu Serum
Inhibiting Enkephalin Degrading Enzymes: Ebikolwa by’ebirungo ebipya ebifuga obulamu ebya peptide Livagen ne Epitalon (Ala-Glu-Asp-Gly) ku nkola ya opioid ez’omunda byasomesebwa, naddala obusobozi bwabyo okukyusa emirimu gya enzymes ezisaanya enkephalin mu serum n’okukwatagana n’ebikwata opioid mu kitundu ky’olususu lw’obutoffaali bw’obwongo. Enkola ya enkephalinase yazuulibwa mu vitro nga tupima omutindo gw’okusaanuuka kw’amazzi ogwa ⊃3;H-Leu-enkephalin nga waliwo peptides ezigezesebwa. Livagen ne Epitalon zaziyiza enziyiza ezisaanya enkephalin mu serum y’omuntu. Bw’ogeraageranya n’eddagala erimanyiddwa ennyo eriziyiza peptidase nga puromycin, leupeptin, ne D-PAM, Livagen yakakasibwa nti ekola bulungi. Enkokola z’ebikolwa eby’okuziyiza ddoozi (dose-inhibition effect curves) eza Livagen ne Epitalon zaali ziwandiikiddwa, era emiwendo gyazo egya IC5⁄2 gyali 20 ne 500 μM [2, 3]..
3. Ebikosa Ebikuuma Ekibumba
Nga Ekirungo Ekiyinza Okukuuma Ekibumba: Okukozesa eddagala lingi mu bakadde kitera okuvaako ekibumba obutakola bulungi. N’olwekyo, ng’emyaka gyeyongera, obulabe bw’okuzimba ekibumba (liver fibrotic induration), obulwadde bw’ekibumba obw’amaanyi n’obw’olubeerera bweyongera. Eno y’ensonga lwaki banoonya eddagala eppya, erikola obulungi era eritali lya bulabe erikuuma ekibumba. Okunoonyereza okumu kulaga nti ekirungo kya hepatic polypeptide complex (Ventvil) ne KEDA tetrapeptide (Lys-Glu-Asp-Ala, Livagen) birina eby’obugagga ebikuuma ekibumba, okukuuma abaserikale b’omubiri, n’okuziyiza okukaddiwa. Mu bikozesebwa mu kugezesa ebisolo ne mu vitro eby’obulwadde bw’ekibumba (kibumba fibrotic induration, acute and chronic hepatitis), Ventvil ne KEDA peptide byalaga obulungi obw’amaanyi. Ventvil ne KEDA peptide zirina ekikolwa ekikwatagana - okuzza embeera y’abaserikale b’omubiri n’obuziyiza obuwuka obuleeta obulwadde mu mbeera eya bulijjo n’okuzzaawo enkola y’ekibumba mu kiseera ky’obulwadde bw’ekibumba. Okunoonyereza kulaga nti mu kiseera ky’okukaddiwa, ebikolwa ebisinga obunene eby’okukuuma ekibumba n’okukuuma obusimu bwa peptides bikakasiddwa [4]..
4. Ebikosa Chromatin ya Lymphocytes
Okukola Chromatin ya Lymphocytes: Ebikolwa bya peptide synthetic Livagen ku nkola y’obuzaale bwa ribosomal, parameters za heterochromatin denaturation, polymorphism ya structural C heterochromatin, n’enkyukakyuka ya facultative heterochromatin mu lymphocytes z’abakadde byasomesebwa. Livagen yaleeta okukola kw’obuzaale bwa ribosomal, okuggya polimeeri y’obuzaale obukola heterochromatin okwetoloola centromere, n’okufulumya obuzaale obwali buziyiziddwa olw’okufuuka kw’ebitundu bya euchromatin ebikwatagana n’emyaka mu chromosomes. Ebivuddemu biraga nti Livagen yaleetawo deheterochromatization (activation) ya chromatin mu chromosomes z’abakadde, ekyatuukibwako nga tukyusa heterochromatin ne heterochromatinized regions mu chromosomes [5]..
Livagen ekozesebwa ki?
Okunoonyereza ku kukaddiwa kw’obutoffaali
Livagen esobola okukosa emirimu gya enzymes enkulu ezenyigira mu kuddaabiriza obutoffaali oba amakubo g’okuddamu ku situleesi. Okugeza, ekwatagana n’abalungamya epigenetic era ne kikwata ku nkyukakyuka mu nsengekera ya chromatin n’engeri y’okwolesebwa kw’obuzaale, bwe kityo ne kifuga enkola y’okukaddiwa kw’obutoffaali. Okwonoonebwa kw’omukka (oxidative damage) kukuŋŋaanyizibwa okumala ekiseera era ne kuleeta obuzibu bw’obutoffaali obuva ku kukaddiwa. Enkola ya Livagen ku kkubo lya oxidative stress kye kimu ku bifo eby’okunoonyereza, era esobola okulwawo okukaddiwa kw’obutoffaali nga etereeza amakubo agakwatagana.
Ebikosa Endwadde z’ekibumba
Ng’emyaka gyeyongera, okukozesa eddagala lingi abakadde kitera okuvaako ekibumba obutakola bulungi, bwe kityo ne kyongera obulabe bw’okuzimba ekibumba, obulwadde bw’ekibumba obw’amaanyi n’obutawona. Mu mbeera eno, kikulu nnyo okuzuula eddagala eppya, erikola obulungi era eritali lya bulabe erikuuma ekibumba. Okunoonyereza okumu kulaga nti ekirungo kya hepatic polypeptide complex (Ventvil) ne KEDA tetrapeptide (Lys-Glu-Asp-Ala, kwe kugamba Livagen) birina eby’obugagga ebikuuma ekibumba, okukuuma abaserikale b’omubiri, n’okuziyiza okukaddiwa. Mu bikolwa eby’okugezesa ebisolo eby’obulwadde bw’ekibumba (ekibumba fibrosis, acute and chronic hepatitis) n’okugezesa mu vitro, Ventvil ne KEDA peptide byalaga obulungi obw’amaanyi. Ventvil ne KEDA peptide zirina ekikolwa eky’okukwatagana, ekiyinza okuzza embeera y’abaserikale b’omubiri n’obuziyiza obuwuka obuleeta obulwadde mu mbeera eya bulijjo n’okuzzaawo enkola y’ekibumba mu kiseera ky’obulwadde bw’ekibumba. Ekirala, mu kiseera ky’okukaddiwa, ebikolwa by’okukuuma ekibumba n’okukuuma obusimu bw’omubiri ebya peptides zino bituuka ku kigero kyabyo ekisingako [4]..
Ebikosa Genomic Parameters z’abalwadde ba kookolo
Kizuuliddwa nti ensengekera y’obutonde (genome) y’abalwadde ba kookolo w’amabeere ow’omu misuwa (ductal breast cancer) emanyiddwa olw’okumenya kwa DNA okw’omuguwa ogumu, emirundi mingi egy’obutabeera bulungi mu nsengekera y’obutonde (chromosomal abnormalities), n’okweyongera kw’omutindo gw’okusengejja kwa chromatin. Okukozesa oligopeptide bioregulator Livagen ne cobalt ions nga modifiers kirina ekikolwa eky’obukuumi ku lymphocyte cultures z’abalwadde ba ductal breast cancer, ekiyinza oku normalize parameters zonna ezisomeseddwa. Kino kiraga nti okuyita mu kunoonyereza ku lymphocytes z’abalwadde abalina kookolo w’amabeere ow’omu misuwa, ekikolwa eky’okuwonya eky’obujjanjabi bw’abalwadde ba kookolo w’amabeere kisobola okwekenneenyezebwa [6]..
Ebikosa Lymphocytes z’abalwadde abalina Hypertrophic Cardiomyopathy n’abooluganda lwabwe
Ebikolwa bya peptide bioregulator Livagen (Lys-Glu-Asp-Ala) ekozesebwa yokka era nga egattibwa wamu ne cobalt ions ku mirimu gy’ebitundu ebitegeka nucleolar (NORs) n’emirundi gy’okukwatagana kwa acrocentric chromosomes mu lymphocytes z’abalwadde abalina hypertrophic cardiomyopathy n’abooluganda lwabwe byasomesebwa. Ebivuddemu biraga nti ekikolwa kya Livagen ne cobalt ions nga kigatta kyayongera ku mirundi gya NORs nga obubonero bungi bwa 2 mu balwadde n’abooluganda lwabwe. Ebirungo bino era byalina kinene kye byakola ku mulimu gw’okukwatagana ogwa acrocentric chromosomes, okweyoleka ng’okweyongera okw’amaanyi mu muwendo guno mu bibinja byombi eby’okunoonyereza.
Mu mbeera eno, ekikolwa kya Livagen ne cobalt ions kyali kikola bulungi. Okuva emirimu gya NORs n’emirundi gy’okukwatagana kwa chromosomes za acrocentric bwe bisinziira ku mutindo gw’okufuumuuka kw’ebikoola bya chromosomes za acrocentric, kiyinza okumalirizibwa nti Livagen ne cobalt ions birina kye bikola ku lymphocytes z’abalwadde abalina hypertrophic cardiomyopathy n’abooluganda lwabwe, ekivaako okusaanuuka kwa heterochromatinized chromatin. Eno eyinza okuba embeera y’okufulumya obuzaale obutakola mu kiseera ky’enkola y’okufuumuuka mu bantu ssekinnoomu ab’ekibinja ky’okunoonyereza. Ebiwandiiko bino biwa amawulire amapya ku bikolwa eby’obukuumi ebya Livagen ne Livagen + cobalt ions ku lymphocytes z’abalwadde abalina hypertrophic cardiomyopathy n’abooluganda lwabwe era ziyinza okuyamba mu kukola enkola z’obujjanjabi [7]..
Ebikosa Enkephalin Degrading Enzymes mu Serum
Ebikolwa by’ebirungo ebipya ebifuga obulamu bwa peptide Livagen (Lys-Glu-Asp-Ala) ne Epitalon (Ala-Glu-Asp-Gly) ku nkola ya opioid ez’omunda byasomesebwa naddala obusobozi bwabyo okukyusa emirimu gy’enziyiza ezisaanya enkephalin mu serum n’okukwatagana n’ebikwata opioid mu kitundu ky’olususu lw’obutoffaali bw’obwongo. Okugezesa mu vitro kwazuula emirimu gya enkephalinase nga bapima omutindo gw’okusaanuuka kw’amazzi ogwa ⊃3;H-Leu-enkephalin nga waliwo Livagen ne Epitalon. Ebyavudde mu kunoonyereza biraga nti Livagen ne Epitalon ziziyiza enziyiza ezisaanya enkephalin mu serum y’omuntu. Livagen yali ekola bulungi okusinga ezimu ezimanyiddwa ennyo eziziyiza peptidase nga puromycin, leupeptin, ne D-PAM. Ebipimo by’ebikolwa eby’okuziyiza ddoozi ebya Livagen ne Epitalon byalagibwa, era emiwendo gyabyo egya IC5⁄2 gyali 20 ne 500 μM. Enkolagana wakati wa peptides ne opioid receptors yatunuulirwa nga tukozesa enkola ya radioligand receptor ne [⊃3;H][D-Ala⊃2;, D-Leu5]-enkephalin. Tewali nkolagana yalabibwa wakati w’ebikwata opioid μ oba δ mu kitundu ky’olususu lw’obwongo bw’envunza ne peptides ezigezesebwa [2, 3]..
Mu kumaliriza, nga elungamya okulaga kw’obuzaale n’okutumbula okukola puloteyina, Livagen eraga ebikolwa ebinene mu kulwanyisa okukaddiwa, okukyusa obusimu obuziyiza endwadde, n’okukuuma enkola y’ekibumba. Kisobola okulungamya emirimu gy’enziyiza z’okugaaya emmere, okuziyiza enziyiza ezisaanya enkephalin, n’okulwawo okukaddiwa kw’obutoffaali nga kikola enziyiza enkulu n’okukwata ekkubo ly’okunyigirizibwa okw’okwokya. Okugatta ku ekyo, Livagen era erongoosa enkola y’abaserikale b’omubiri n’embeera y’ekirungo ekiziyiza obuwuka obuleeta obulwadde bw’ekibumba ng’eyita mu nkola yaayo ey’okukuuma ekibumba n’okutumbula okuddamu okukola kw’ekibumba mu ndwadde ng’obulwadde bw’ekibumba. Kirina omugaso oguyinza okukozesebwa mu kuziyiza n’okujjanjaba endwadde ezikwatagana era kiwa obulagirizi obupya obw’okunoonyereza ku kulwanyisa okukaddiwa n’okukuuma obulamu.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Vladimir Khavinson yali musawo wa bakadde era pulofeesa omututumufu mu Russia amanyiddwa olw’okunoonyereza kwe okwasooka mu bikozesebwa mu kutereeza ebiramu ebiyitibwa peptide bioregulators n’omulimu gwabyo mu kukendeeza ku kukaddiwa n’okutumbula obulamu. Yaweereza nga dayirekita w’ekitongole kya St. Petersburg Institute of Bioregulation and Gerontology era nga yali mmemba akwatagana n’ekibiina kya Russian Academy of Sciences. Okunoonyereza kwe kwasinga kukwata ku kukola obujjanjabi obusinziira ku peptide okutumbula enkola y’abaserikale b’omubiri, okukuuma situleesi ya oxidative, n’okutumbula okuwangaala. Mu myaka amakumi ana, yaggyamu n’akola ebirungo ebingi ebiyitibwa peptide complexes, ekyaviirako okuleeta eddagala mukaaga eryesigamiziddwa ku peptide n’emmere 64 ey’emmere ey’ekika kya peptide mu nkola y’obujjanjabi. Omulimu gwa Khavinson guyambye nnyo mu kisaawe ky’eby’obukadde naddala mu kutegeera enkola z’okukaddiwa n’okukola ebikolwa okutumbula omutindo gw’obulamu mu bantu abakadde.
Vladimir Khavinson mukugu mu by’obukadde era pulofeesa omututumufu mu Russia, amanyiddwa nnyo olw’okunoonyereza kwe okutandikawo enkola ya peptide bioregulators n’omulimu gwazo mu kuziyiza okukaddiwa n’okutumbula obulamu. Yalina ekifo kya dayirekita mu ttendekero lya St. Petersburg Institute of Bioregulation and Gerontology era nga yali mmemba akwatagana n’ekitongole kya Russian Academy of Sciences. Okunoonyereza kwe kwali kwesigamye ku kukola obujjanjabi obusinziira ku peptide okutumbula enkola y’abaserikale b’omubiri, okuziyiza situleesi ya oxidative, n’okuyamba okuwangaala. Mu myaka egisukka mu makumi ana egy’okunoonyereza, yaggyamu n’akola ebirungo eby’enjawulo ebiyitibwa peptide complexes, ekyatumbula okukozesa eddagala mukaaga erikolebwa mu peptide mu bujjanjabi n’emmere 64 eyesigamiziddwa ku peptide. Omulimu gwa Khavinson gukoze kinene mu kisaawe ky‟eby‟obukadde naddala mu kutegeera enkola z‟okukaddiwa n‟okukola enkola z‟okuyingira mu nsonga okutumbula omutindo gw‟obulamu bw‟abakadde. Vladimir Khavinson awandiikiddwa mu kiwandiiko ekijuliziddwa [5].
