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1kits （10Ibikoresho）
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Imiterere Epi ya
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: Epita |
Epibwa Ubushakashatsi
Ni ubuhe bushakashatsi bwakozwe na Epi?
Mu myaka ya za 1980, itsinda ry’abashakashatsi b’Uburusiya bayobowe na Vladimir Khavinson bavumbuye bwa mbere Epi1 [1] . Epi ni peptide ngufi igizwe na acide enye za amine: alanine, aside glutamic, aside aside, na glycine. Synthesis yayo ishingiye kuri peptide naturel epithalamion yakuwe muri glande. Epi bemeza ko igira ingaruka za antioxydeant igereranywa na melatonine kandi ishobora kugira inyungu zo kongera igihe [2] . Abashakashatsi basanze Epi 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, Epi irashobora gufasha kwagura telomereri, bityo bikadindiza gusaza no kwirinda indwara ziterwa no gusaza [1] . Ubushakashatsi bumwe bwerekanye ko Epi 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 Epi (Ala-Glu-Asp-Gly) irashobora kugira ingaruka zo kurwanya gusaza mu guhagarika izo genes. Hamwe na hamwe, Epi 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 Epi bwibanze cyane ku cyiciro cy’igeragezwa ry’inyamaswa, kandi imikorere yacyo n’igihe kirekire n’umutekano mu bantu ntabwo byamenyekanye neza. Nubwo ubushakashatsi bw’inyamaswa bwageze ku bisubizo bishimishije, nko mu nzoka, Epi ifitanye isano no kubaho igihe kirekire ndetse n’ubuzima bwiza, ikoreshwa ry’ibisubizo ku bantu riracyasaba ubundi bushakashatsi [1].
Nubuhe buryo bwibikorwa bya Epi murwego 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 Epi ishobora kugabanya umuvuduko wo gutandukanya cytoplasmeque ya oocytes iterwa no gusaza hamwe nibiri mu bwoko bwa ogisijeni yo mu bwoko bwa reaction ya ogisijeni [2] . Nka antioxydeant, Epi 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. Epi irashobora kuba ifite ubushobozi bwo kwitwara neza na ROS no kuyihindura mubintu bitagira ingaruka. Icya kabiri, kuzamura ibikorwa bya enzymes za antioxydeant. Epi irashobora gukangura ibikorwa byimisemburo ya antioxydants ya 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. Epi 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. Epi irashobora kongera ubushobozi bwa mitochondrial membrane igenga imiyoboro ya ion cyangwa gutwara proteyine 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. Epi irashobora kongera 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. Epi irashobora kugabanya ibipimo bya morphologie idasanzwe na exocytose idasanzwe ya cortical granules [2] . Ibi birashobora guterwa ningaruka zoguhindura Epi 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. Epi 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. Epi irashobora kugumana ituze rya cortical granules muguhindura uburyo bwimikorere ya selile 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. Epi irashobora kugabanya igipimo cyiza cya Annexine V irangi hamwe nuburemere bwa fluorescence ya γH2AX muri vitro oocytes ishaje [2] . Ibi byerekana ko Epi ishobora kugabanya apoptose ya oocytes. Uburyo bwihariye bushobora kubamo: Icya mbere, kubuza inzira ya apoptose yerekana inzira. Epi irashobora kubuza kwanduza ibimenyetso bya apoptose mugutunganya poroteyine zingenzi mumihanda yerekana ibimenyetso bya apoptose, nka proteine z'umuryango wa Bcl-2 na proteine z'umuryango wa caspase, kandi bikagabanya urupfu rw'uturemangingo. Icya kabiri, kubungabunga umutekano wa genomic. γH2AX ni kimwe mu bimenyetso byangiza ADN. Epi irashobora kugumana ituze rya genoside igabanya kwangirika kwa ADN no kugabanya ibimenyetso bya apoptose.
Epi yagumanye ubunyangamugayo busanzwe no gukwirakwiza CGs.
Inkomoko: Byatangajwe [2]
Nubuhe buryo bwihariye bwibikorwa bya Epi mukuvura indwara zifata ubwonko?
Kugena imikorere yubudahangarwa:
Ubushakashatsi bwerekanye ko Epi ishobora kugira ingaruka kumubiri wimbeba mubihe bitandukanye. Imbere yo guhangayikishwa no gukingira indwara hamwe na immunosuppressive ihuriweho hamwe, Epi irashobora kongera ibikorwa byo gukwirakwiza thymocytes [4] . Ibi bivuze ko Epi ishobora kongera imbaraga z'umubiri kurwanya indwara zifata ubwonko zigenga umubiri. 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 Epi ku ikwirakwizwa rya thymocytes zirashobora gufasha kugumana uburinganire bwimikorere yumubiri, bityo bikagabanya ibimenyetso byindwara zifata ubwonko.
Ingaruka ku kimenyetso cyo guhererekanya ibimenyetso:
Epi igira ingaruka zingirakamaro kuri interleukin-1β (IL-1β) inzira yo gutambutsa ibimenyetso. By'umwihariko, Epi irashobora kongera imbaraga zo guhuza imbaraga za IL-1β kandi ikagira ingaruka ku bikorwa bya enzyme y'ingenzi mu nzira yo kwanduza ibimenyetso bya ceramide mu nzira yo mu bwonko bwa cortex, ni ukuvuga membrane itabogamye sphingomyelinase (nSMase) [4] . IL-1β ni cytokine yingenzi igira uruhare muburyo butandukanye bwa physiologique na patologi. Mu ndwara zifata ubwonko, imvugo idasanzwe ya IL-1β irashobora gutera neuroinflammation no kwangirika kwa neuronal. Mugutegeka inzira ya transduction ya IL-1β, Epi irashobora kugabanya neuroinflammation kandi ikarinda neuron kwangirika. Mubyongeyeho, impinduka mubikorwa bya nSMase nazo zifitanye isano n'indwara zifata ubwonko. Amabwiriza yibikorwa bya nSMase na Epi arashobora gufasha kugumana imikorere isanzwe yingirabuzimafatizo.Mu gusoza, uburyo bwibikorwa bya Epi mukuvura indwara zifata ubwonko bushobora kuba bukubiyemo kugenzura ubudahangarwa no kugenzura inzira yo kwanduza ibimenyetso. Nyamara, ubushakashatsi buriho kuri Epi mu kuvura indwara zifata ubwonko buracyari mu ntangiriro, kandi harakenewe ubundi bushakashatsi kugira ngo hemezwe ko bukora neza n'umutekano.
Iterambere ryubushakashatsi bwa Epi
Ingaruka ku bwiza bwa oocytes
Gutinda gusaza kwa oocytes:
Mu bushakashatsi bwakozwe na vitro bwerekanye ko Epi 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, Epi ikora kimwe na melatonine kandi ni antioxydants ikora neza, ishobora kugira inyungu zo kongera igihe. Umuti hamwe na Epi wagabanije cyane inshuro zinenge za spindle no gukwirakwiza bidasanzwe granules ya cortique mugihe cyamasaha 12 namasaha 24 yo gusaza, kandi icyarimwe byongereye mitochondrial membrane ubushobozi hamwe na kopi ya ADN ya mitochondial, bityo bigabanya apoptose ya oocytes mugihe cyamasaha 24 yo gusaza kwa vitro. Ibisubizo byerekana ko Epi ishobora gutinza gusaza kwa oocytes muri vitro muguhuza ibikorwa bya mitochondial na ROS urwego [2].
Kuzamura ireme rya oocytes:
Ongeraho 0.1 mM ya Epi 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 ubukana bwa mitochondrial membrane na vitro ya vitamine ya Annex. oocytes. Ibi byerekana ko Epi ishobora kunoza imitekerereze 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 (Epi) ishobora kongera synthesis yerekana ibimenyetso bitandukanya neurogenic mu ngirabuzimafatizo ya gingival mesenchymal stem selile, nka Nestin, GAP43, β Tubulin III, na Doublecortin. Uburyo bwo kwerekana imiterere ya molekulari bwerekana ko Epi ikunda guhuza amateka ya H1 / 6 na H1 / 3, ishobora kuba imwe muburyo bwo kongera iyandikwa ryiyi genes itandukanya neuronal [5].
Ingaruka igenga sisitemu y'imitsi
Kugenga ibikorwa bya neuronal:
Binyuze mu bushakashatsi bwakozwe ku mbeba, byagaragaye ko kwinjiza Epi (2 ng) bishobora gukora cyane mu mikorere y’imitsi y’ubwonko bw’ubwonko bw’imbeba mu minota mike, kandi inshuro zo kurasa za neuron zikiyongera inshuro 2 - 2,5 [6] . Mu byafashwe amajwi bimwe, ibisubizo bigoye bigizwe nibyiciro byinshi nabyo byagaragaye. Ubwiyongere bwibikorwa byizana bya neuron na Epi biterwa numurongo mwinshi wibice bimaze gukora kandi uruhare rwama selile yacecetse. Nibura icyiciro cya mbere cyibikorwa bya Epi gishobora gusobanurwa ningaruka itaziguye yiyi peptide kuri selile ya cortex.
Ingaruka zo gukingira:
Epi igira ingaruka zo kurinda imbeba guhura nibibazo bitandukanye. Ubushakashatsi bwerekanye ko Epi yongera ibikorwa byo gukwirakwiza thymocytes. Yaba yongerewe imbaraga mu guhangayikishwa no gukingira indwara cyangwa guhagarikwa mu gihe cyo gukingira indwara, Epi irashobora kugira uruhare mu kugenzura (Vladimir Kh Khavinson, 2002). Muri icyo gihe, Epi irashobora kandi kongera imbaraga zo guhuza interleukin-1β (IL-1β) kandi ikagira ingaruka ku mpinduka mu bikorwa bya sphingomyelinase (nSMase) mu bwonko bwubwonko bwatewe no guhangayika. Ibi byerekana ko Epi 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, Epi irashobora kugabanya urwego rwibanze rwa glucose na insuline kandi ikongera urugero rwa melatonine nijoro. Muri icyo gihe, Epi 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 Epi ari ikintu cyiza cyo kugarura imikorere mibi ya endocrine idakora neza muri primates [7].
Ikoreshwa rya Epi 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. Epi irashobora guteza imbere ikwirakwizwa no gutandukanya ingirabuzimafatizo zikomeye, kongera umubare wa neuron, no kunoza imikorere yubwenge bw’abarwayi ba Alzheimer. Byongeye kandi, Epi 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. Epi irashobora guteza imbere ikwirakwizwa ry’imitsi n’ingirabuzimafatizo, ikongera umubare wa neuron ya dopaminergique, ikanatezimbere imikorere y’imodoka 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. Epi irashobora guteza imbere ikwirakwizwa no gutandukanya ingirangingo ngengabuzima, kongera umubare wa neuron, no kunoza imikorere y’imyakura y’abarwayi b’imitsi n’ubwonko [8].
Mu gusoza, nka tetrapeptide ya syntetique, uburyo bwibanze bwo kurwanya gusaza kwa Epi 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 yambere 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].
