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Imiterere ya Epitalon Structure
Inkomoko: PubChem |
Urukurikirane: Ala-Glu-Asp-Gly Inzira ya molekulari: C 14H 22N 4O.9 Uburemere bwa molekuline: 390.35 g / mol Numero ya CAS: 307297-39-8 PubChem CID: 219042 Synonyme: Epithalon |
Research bwa Epitalon Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na Epitalon?
Mu myaka ya za 1980, itsinda ry’abashakashatsi b’Uburusiya bayobowe na Vladimir Khavinson bavumbuye bwa mbere Epitalon1 [1] . Epitalon ni peptide ngufi igizwe na acide enye za amine: alanine, aside glutamic, aside aspartic, na glycine. Synthesis yayo ishingiye kuri peptide naturel epithalamion yakuwe muri glande. Epitalon bemeza ko igira ingaruka za antioxydeant igereranywa na melatonine kandi ishobora kugira inyungu zo kongera igihe [2] . Abashakashatsi basanze Epitalon ishobora gukangura ibikorwa bya telomerase. Telomerase ni enzyme ishobora kurinda no kwagura telomereri kumpera ya chromosomes. Iyo abantu basaza, telomeres igabanya, ifitanye isano n'indwara ziterwa n'imyaka hamwe no kubaho igihe gito. Mugukangura ibikorwa bya telomerase, Epitalon irashobora gufasha kwagura telomereri, bityo bikadindiza gusaza no kwirinda indwara ziterwa no gusaza [1] . Ubushakashatsi bumwe bwerekanye ko Epitalon ishobora kugira uruhare mu kugenzura imiterere ya gen CCL11 na HMGB1 kandi ikagira uruhare mu kwerekana izo genes. Muri icyo gihe, villa ya dipeptide (Lys-Glu) na tetrapeptide Epitalon (Ala-Glu-Asp-Gly) irashobora kugira ingaruka zo kurwanya gusaza mu guhagarika izo genes. Hamwe na hamwe, Epitalon na vilon bizwiho kugenga imiterere ya gene hamwe na sintezamubiri ya poroteyine, bigatuma igabanuka ry’imfu ndetse n’iterambere ridindiza iterambere ry’abasaza [3] . Kugeza ubu, ubushakashatsi kuri Epitalon bwibanze cyane ku cyiciro cy’igeragezwa ry’inyamaswa, kandi ingaruka zacyo n’umutekano muremure mu bantu ntabwo byamenyekanye neza. Nubwo ubushakashatsi bwibikoko bimwe na bimwe bwageze ku bisubizo bishimishije, nko mu nzoka, Epitalon ifitanye isano no kubaho igihe kirekire ndetse n’ubuzima bwiza, ikoreshwa ry’ibisubizo ku bantu riracyasaba ubundi bushakashatsi [1].
Ni ubuhe buryo bwo gukora bwa Epitalon mu rwego rwo kurwanya gusaza?
Kugabanya urwego rwubwoko bwa ogisijeni ikora:
Ubwoko bwa ogisijeni ikora (ROS) igira uruhare runini mugusaza kwa oocytes. ROS ikabije izatera okiside yangiza oocytes, igire ingaruka nziza hamwe niterambere ryiterambere. Ubushakashatsi bwerekanye ko Epitalon ishobora kugabanya umuvuduko wo gucamo cytoplazimike ya oocytes iterwa no gusaza ndetse n'ibiri mu bwoko bwa ogisijeni yo mu bwoko bwa reaction ya ogisijeni [2] . Nka antioxydeant, Epitalon irashobora gutesha agaciro ROS yo mu nda no kugabanya ibyangiritse kuri oocytes. By'umwihariko, birashobora kugerwaho muburyo bubiri bukurikira: Icya mbere, gusiba ROS mu buryo butaziguye. Epitalon irashobora kugira ubushobozi bwo kwitwara neza na ROS no kuyihindura mubintu bitagira ingaruka. Icya kabiri, kuzamura ibikorwa bya enzymes za antioxydeant. Epitalon irashobora gukangurira ibikorwa byimisemburo ya antioxyde-antioxydeant, nka superoxide dismutase (SOD), catalase (CAT), nibindi. Iyi misemburo irashobora gufasha gusiba ROS no kugumana uburinganire bwimitsi itukura.
Kunoza imikorere ya mitochondial:
Mitochondriya igira uruhare runini mu mbaraga za metabolism no kubaho kwa oocytes. Mugihe oocytes isaza, imikorere ya mitochondial izagenda igabanuka buhoro buhoro, bigaragazwa nkigabanuka ryimbaraga za mito-iyambere ndetse no kugabanuka kwa kopi ya ADN ya mito-iyambere. Epitalon irashobora kongera ubushobozi bwa mitochondrial membrane hamwe na kopi ya ADN ya mitochondial [2] . Ibi bifasha kunoza ingufu za oocytes no gukomeza imikorere isanzwe ya physiologique ya selile. Uburyo bwihariye bwibikorwa bushobora kubamo: Icya mbere, kongera ubushobozi bwa mitochondrial membrane. Kugumana ubushobozi bwa mitochondrial membrane ni ingenzi kumikorere isanzwe ya mitochondria. Epitalon irashobora kongera ubushobozi bwa mitochondrial membrane igenga imiyoboro ya ion cyangwa gutwara poroteyine kuri membrane ya mitochondrial, bikongerera ingufu ingufu za mitochondriya. Icya kabiri, kongera umubare wa kopi ya ADN ya mitochondial. Kongera umubare wa kopi ya ADN ya mitochondrial ADN birashobora kunoza ubushobozi bwa synthesis ya mitochondria kandi bigatanga ingufu nyinshi kuri selile. Epitalon irashobora kongera umubare wa kopi ya ADN ya mitochondial iteza imbere kwigana ADN ya mitochondial cyangwa kugabanya iyangirika ryayo.
Kugabanya morfologiya idasanzwe na exocytose idasanzwe ya cortical granules:
Mugihe cyo gusaza kwa oocytes, ibipimo bya morphologie idasanzwe ya spindle na exocytose idasanzwe ya cortical granules iziyongera, ibyo bizagira ingaruka kumasemburo hamwe nubushobozi bwo gukura kwa oocytes. Epitalon irashobora kugabanya ibipimo bya morphologie idasanzwe na exocytose idasanzwe ya cortical granules [2] . Ibi birashobora guterwa ningaruka zoguhindura Epitalon kumitekerereze ya cytoskeleton na membrane selile: Icya mbere, guhagarika imiterere ya spindle. Spindle ni imiterere yingenzi mugikorwa cyo kugabana selile, kandi morphologie yayo idasanzwe izatuma habaho gutandukana kwa chromosome bidasanzwe kandi bigira ingaruka kumikurire ya oocytes. Epitalon irashobora guhagarika imiterere ya spindle muguhindura polymerisation na depolymerisation ya tubuline, bikagabanya kubaho kwa morphologie idasanzwe. Icya kabiri, kubungabunga ituze rya cortical granules. Cortical granules igira uruhare runini mugikorwa cyo gusama oocytes. Epitalon irashobora kugumya gukomera kwa cortical granules muguhindura uburyo bwimikorere ya selile cyangwa calcium ion yerekana ibimenyetso, bikagabanya kubaho kwa exocytose idasanzwe.
Kugabanya ibimenyetso bya apoptose:
Mugihe cyo gusaza kwa oocytes, ibimenyetso bya apoptose biziyongera, biganisha ku rupfu. Epitalon irashobora kugabanya umuvuduko mwiza wa Annexine V hamwe nuburemere bwa fluorescence ya γH2AX muri vitro oocytes ishaje [2] . Ibi byerekana ko Epitalon ishobora kugabanya apoptose ya oocytes. Uburyo bwihariye bushobora kubamo: Icya mbere, kubuza inzira ya apoptose yerekana inzira. Epitalon irashobora kubuza kwanduza ibimenyetso bya apoptose muguhindura poroteyine zingenzi mu nzira yerekana ibimenyetso bya apoptose, nka poroteyine z'umuryango wa Bcl-2 na poroteyine z'umuryango wa caspase, kandi bikagabanya imfu z'utugingo. Icya kabiri, kubungabunga umutekano wa genomic. γH2AX ni kimwe mu bimenyetso byangiza ADN. Epitalon irashobora kugumana ituze rya genoside igabanya kwangirika kwa ADN no kugabanya ibimenyetso bya apoptose.
Epitalon yagumanye ubusugire busanzwe no gukwirakwiza CGs.
Inkomoko: Byatangajwe [2]
Nubuhe buryo bwihariye bwibikorwa bya Epitalon mukuvura indwara zifata ubwonko?
Kugena imikorere yubudahangarwa:
Ubushakashatsi bwerekanye ko Epitalon ishobora kugira ingaruka kumubiri wimbeba mubihe bitandukanye. Imbere yo guhangayikishwa no gukingira indwara hamwe na immunosuppressive ihuriweho hamwe, Epitalon irashobora kongera ibikorwa byo gukwirakwiza thymocytes [4] . Ibi bivuze ko Epitalon ishobora kongera umubiri kurwanya indwara zifata ubwonko muguhindura sisitemu yumubiri. Ikwirakwizwa rya thymocytes rifitanye isano rya bugufi n’imikorere ya sisitemu y’umubiri, kandi sisitemu y’umubiri igira uruhare runini mu kubaho no guteza imbere indwara zifata ubwonko. Kurugero, indwara zimwe na zimwe zifata ubwonko zishobora kuba zifitanye isano no gukora bidasanzwe cyangwa imikorere mibi yumubiri. Ingaruka zitera Epitalon ku ikwirakwizwa rya thymocytes zirashobora gufasha kugumana uburinganire bwimikorere yumubiri, bityo bikagabanya ibimenyetso byindwara zifata ubwonko.
Ingaruka ku kimenyetso cyo guhererekanya ibimenyetso:
Epitalon igira ingaruka zingirakamaro kuri interleukin-1β (IL-1β) inzira yo gutambutsa ibimenyetso. By'umwihariko, Epitalon irashobora kongera imbaraga za IL-1β kandi ikagira ingaruka kumikorere ya enzyme yingenzi mumihanda ya ceramide yerekana inzira yo kwanduza ubwonko bwubwonko bwubwonko, aribwo membrane itabogamye sphingomyelinase (nSMase) [4] . IL-1β ni cytokine yingenzi igira uruhare muburyo butandukanye bwa physiologique na patologi. Indwara zifata ubwonko, imvugo idasanzwe ya IL-1β irashobora gutera neuroinflammation no kwangirika kwa neuronal. Mugutegeka inzira ya transduction ya IL-1β, Epitalon irashobora kugabanya neuroinflammation kandi ikarinda neuron kwangirika. Mubyongeyeho, impinduka mubikorwa bya nSMase nazo zifitanye isano n'indwara zifata ubwonko. Amabwiriza yibikorwa bya nSMase na Epitalon arashobora gufasha kugumana imikorere isanzwe yingirabuzimafatizo.Mu gusoza, uburyo bwibikorwa bya Epitalon mukuvura indwara zifata ubwonko bushobora kuba bukubiyemo kugenzura ubudahangarwa no kugenzura inzira yo kwanduza ibimenyetso. Nyamara, ubushakashatsi buriho kuri Epitalon mu kuvura indwara zifata ubwonko buracyari mu ntangiriro, kandi haracyakenewe ubundi bushakashatsi kugira ngo hemezwe neza n'umutekano.
Iterambere ryubushakashatsi bwa Epitalon
Ingaruka ku bwiza bwa oocytes
Gutinda gusaza kwa oocytes:
Mu bushakashatsi bwakozwe na vitro bwerekanye ko Epitalon ishobora kugabanya urwego rwimiterere ya ogisijeni yo mu bwoko bwa ogisijeni (ROS) muri oocytes yimbeba ishaje nyuma yintanga. Igihe kirenze, ubushobozi bwiterambere bwa oocytes buzagenda bugabanuka buhoro buhoro nyuma yintanga muri vivo cyangwa muri vitro. Nka peptide ngufi ya peptide, Epitalon ikora kimwe na melatonine kandi ni antioxydants ikora neza, ishobora kugira inyungu zo kongera igihe. Umuti hamwe na Epitalon wagabanije cyane inshuro zinenge za spindle no gukwirakwiza bidasanzwe granules cortique mugihe cyamasaha 12 namasaha 24 yo gusaza, kandi icyarimwe byongereye ubushobozi bwa mitochondrial membrane na kopi ya ADN ya mitochondial, bityo bigabanya apoptose ya oocytes mugihe cyamasaha 24 yo gusaza kwa vitro. Ibisubizo byerekana ko Epitalon ishobora gutinza gusaza kwa oocytes muri vitro muguhindura ibikorwa bya mitochondial na ROS urwego [2].
Kuzamura ireme rya oocytes:
Ongeraho 0.1 mM ya Epitalon muburyo bwa vitro umuco urashobora kugabanya umuvuduko wo gucamo ibice bya cytoplasmeque mugikorwa cya parthenogenetike ya oocytes iterwa no gusaza kwa vitro nyuma yo gutera intanga, kugabanya igipimo cyimiterere idasanzwe ya spindle morphologie na exocytose idasanzwe ya granules cortique, kongera umubare wa mitochondrial membrane na vitamine ya vitamine ya XX. oocytes ishaje. Ibi byerekana ko Epitalon ishobora kunoza imiterere ya organelles mugihe cya vitro yo gusaza kwa oocytes no kuzamura ireme rya oocytes (Xue Yue).
Ingaruka ku gutandukanya ingirabuzimafatizo
Ubushakashatsi bwerekanye ko peptide ya AEDG (Epitalon) ishobora kongera synthesis yerekana ibimenyetso bitandukanya neurogenic mu ngirabuzimafatizo ya gingival mesenchymal, nka Nestin, GAP43, β Tubulin III, na Doublecortin. Uburyo bwo kwerekana imiterere ya molekuline bwerekana ko Epitalon ihitamo cyane amateka ya H1 / 6 na H1 / 3, ishobora kuba imwe muburyo bwo kongera iyandikwa rya genes zitandukanya neuronal [5].
Ingaruka igenga sisitemu y'imitsi
Kugenga ibikorwa bya neuronal:
Binyuze mu bushakashatsi bwakozwe ku mbeba, byagaragaye ko kwinjiza intitalasal Epitalon (2 ng) bishobora gukora cyane ibikorwa byubwonko bwubwonko bwubwonko bwimbeba mu minota mike, kandi inshuro zo kurasa za neuron ziyongera inshuro 2 - 2,5 [6] . Mu byafashwe amajwi bimwe, ibisubizo bigoye bigizwe nibyiciro byinshi nabyo byagaragaye. Ubwiyongere bwibikorwa byizana bya neuron na Epitalon biterwa numurongo mwinshi wibice bimaze gukora ndetse no kwitabira selile zacecetse. Nibura icyiciro cya mbere cyibikorwa bya Epitalon gishobora gusobanurwa ningaruka itaziguye yiyi peptide kuri selile ya cortex.
Ingaruka zo gukingira:
Epitalon igira ingaruka zo kurinda imbeba guhura nibibazo bitandukanye. Ubushakashatsi bwerekanye ko Epitalon yongera ibikorwa byo gukwirakwiza thymocytes. Byaba byongerewe imbaraga mu guhangayikishwa no gukingira indwara cyangwa kubuzwa guhangayikishwa no gukingira indwara, Epitalon irashobora kugira uruhare mu kugenzura (Vladimir Kh Khavinson, 2002). Muri icyo gihe, Epitalon irashobora kandi kongera imbaraga zo guhuza interleukin-1β (IL-1β) kandi ikagira ingaruka ku ihinduka ryibikorwa bya sphingomyelinase (nSMase) mu bwonko bwubwonko bwatewe no guhangayika. Ibi byerekana ko Epitalon igira ingaruka zo kurinda ihungabana kurwego rwa IL-1β kwanduza ibimenyetso mu nzira ya sphingomyelin no kurwego rwo gukwirakwiza thymocyte mu myanya myakura.
Ingaruka kumikorere ya endocrine ya primates zitari abantu:
Inkende zishaje za rhesus, Epitalon irashobora kugabanya urwego rwibanze rwa glucose na insuline kandi ikongera urugero rwa melatonine nijoro. Muri icyo gihe, Epitalon irashobora kugabanya agace kari munsi yumurongo wa plasma glucose, ikongera igipimo cya 'kubura ' cya glucose, kandi igahindura plasma insuline kinetics isubiza ubuyobozi bwa glucose. Ibi byerekana ko Epitalon ari ikintu cyiza cyo kugarura imikorere mibi ya endocrine idakora neza muri primates [7].
Ikoreshwa rya Epitalon mukuvura indwara zifata imitsi
Indwara ya Alzheimer: Indwara ya Alzheimer n'indwara ikunze kwibasira neurodegenerative, ahanini irangwa no kugabanuka kw'imikorere y'ubwenge no guta umutwe. Ubushakashatsi buriho bwerekana ko indwara ya Alzheimer ifitanye isano no gutandukana kwa neurogeneque. Umubare w'uturemangingo ngengabuzima mu bwonko bw'abarwayi ba Alzheimer uragabanuka, kandi ubushobozi bwabo bwo gutandukanya nabwo burabujijwe. Epitalon irashobora guteza imbere ikwirakwizwa ry'uturemangingo ngengabuzima, kongera umubare wa neuron, no kunoza imikorere yo kumenya abarwayi ba Alzheimer. Byongeye kandi, Epitalon irashobora kandi kugenga irekurwa rya neurotransmitter, ikongera ubushobozi bwo kwibuka no kwiga by’abarwayi ba Alzheimer [8].
Indwara ya Parkinson: Indwara ya Parkinson n'indwara ya neurodegenerative ahanini irangwa n'indwara ya moteri. Ikintu nyamukuru kiranga indwara ni ugutakaza neuron ya dopaminergique muri nigra. Uburyo bwo kuvura ubu bugabanya cyane cyane ibimenyetso byongera dopamine cyangwa bikabuza kwangirika kwa dopamine, ariko ubu buryo ntibushobora guhagarika iterambere ryindwara. Guhindura ingirabuzimafatizo ya selile nuburyo bwo kuvura, ariko inkomoko nubushobozi bwo gutandukanya ingirabuzimafatizo zikomeye ziracyari ikibazo. Epitalon irashobora guteza imbere gukwirakwiza no gutandukanya ingirabuzimafatizo ngengabuzima, kongera umubare wa neuron ya dopaminergique, no kunoza imikorere ya moteri y’abarwayi ba Parkinson [8].
Indwara yo mu bwonko no mu bwonko: Indwara ni indwara ikunze kugaragara mu bwonko, kandi ingaruka zayo nyamukuru ni urupfu rwa neuron no kudakora neza kw'imitsi. Gukomeretsa ubwonko nabyo bishobora gutera kubura neuron no kudakora neza. Ingirabuzimafatizo zikomeye zigira uruhare runini mu gusana no kuvugurura nyuma yubwonko no gukomeretsa ubwonko. Epitalon irashobora guteza imbere ikwirakwizwa ry'uturemangingo ngengabuzima, ikongera umubare wa neuron, kandi igateza imbere imikorere y’imitsi y’abarwayi b’imitsi n’ubwonko [8].
Mu gusoza, nka tetrapeptide ya syntetique, uburyo bwibanze bwo kurwanya gusaza kwa Epitalon bushingiye mugukora imvugo ya telomerase reverse transcriptase subunit (TERT), kwagura uburebure bwa telomereri no gukomeza ibikorwa bya telomerase, bityo bikagira uruhare mubikorwa byingenzi byo gusaza kwa selile. Akamaro kayo kari muburyo bwa mbere bwo gutahura kurwanya gusaza duhereye ku binyabuzima bya telomere, guca ukubiri na antioxydants gakondo yibasira gusa radicals yubuntu, no gutanga intego nshya yo gutinza indwara ziterwa nimyaka nkindwara ya Alzheimer n'indwara z'umutima. Nubwo umutekano wacyo wigihe kirekire (cyane cyane ibyago bya kanseri) uracyakeneye kugenzurwa mugice cya gatatu cyamavuriro yubuvuzi, nkubushakashatsi niterambere ryambere rya telomerase ya mbere ya enterineti yo mu bwoko bwa anti-gusaza, birerekana ko habaye impinduka mu mpinduramatwara mu gusaza kuva mu kunoza ibimenyetso kugeza ku mikorere y’imikorere ya molekile kandi biteganijwe ko bizamura ubuzima bwabo bwa muntu.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru Scientific Vladimir Khavinson ni umuhanga mu bumenyi bw’ibinyabuzima w’Uburusiya akaba n'umushakashatsi wa peptide bioregulator. Ni Umuyobozi w'ikigo cya St. Petersburg Institute of Bioregulation na Gerontology akaba n'umwe mu bagize Ishuri Rikuru ry'Ubuvuzi ry'Uburusiya. Khavinson yagize uruhare runini mu bijyanye n'ubushakashatsi bwo gusaza kandi yanditse ibitabo byinshi mu binyamakuru bizwi nka 'Molecular Biology of Aging ' na 'Ikinyamakuru cyo kurwanya gusaza '. Ibikorwa bye byibanze cyane cyane ku iterambere no gushyira mu bikorwa peptide bioregulators mu kurwanya indwara ziterwa n’imyaka no guteza imbere ubuzima. Ubushakashatsi bwa Khavinson bwagize uruhare runini mubijyanye na gerontologiya, butanga ubumenyi bushya hamwe nuburyo bwo kuvura gusaza neza. Vladimir Khavinson yanditse ku rutonde rw'ibitekerezo [5].
