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▎ Epitalon Structure
Isi mmalite: PubChem |
Usoro: Ala-Glu-Asp-Gly Ụdị mkpụrụ ndụ: C 14H 22N 4O9 Arọ Molecular: 390.35 g/mol Nọmba CAS: 307297-39-8 PubChem CID: 219042 Nkọwa okwu: Epithalon |
▎ Epitalon Nnyocha
Kedu ihe ndabere nyocha nke Epitalon?
N'afọ ndị 1980, otu ndị nchọpụta Russia nke Vladimir Khavinson duziri na mbụ chọpụtara Epitalon1 [1] . Epitalon bụ peptide dị mkpụmkpụ nke sịntetik mejupụtara amino acid anọ: alanine, glutamic acid, aspartic acid na glycine. Ngwakọta ya dabere na peptide epithlamion eke ekepụtara na gland pineal. Ekwenyere na Epitalon nwere mmetụta antioxidant dị ka nke melatonin ma nwee ike ịba uru nke ịgbatị ndụ [2] . Ndị nchọpụta achọpụtala na Epitalon nwere ike ịkpali ọrụ telomerase. Telomerase bụ enzyme nke nwere ike ichebe ma gbasaa telomeres na nsọtụ chromosomes. Ka ndị mmadụ na-eme agadi, telomeres na-ebelata, nke jikọtara ya na ọrịa ndị metụtara afọ na ndụ dị mkpụmkpụ. Site n'ịkwalite ọrụ telomerase, Epitalon nwere ike inye aka ịgbatị telomeres, si otú a na-ebelata usoro ịka nká na igbochi ọrịa ndị metụtara ịka nká [1] . Ụfọdụ ọmụmụ egosila na Epitalon nwere ike itinye aka n'ịhazi okwu nke mkpụrụ ndụ ihe nketa CCL11 na HMGB1 ma mee dị ka onye na-eme ka nkwupụta nke mkpụrụ ndụ ihe nketa ndị a. N'otu oge ahụ, dipeptide vilon (Lys-Glu) na tetrapeptide Epitalon (Ala-Glu-Asp-Gly) nwere ike ịkpata mmetụta mgbochi ịka nká site na igbochi mkpụrụ ndụ ihe nketa ndị a. Ọnụ, a maara Epitalon na vilon na-achịkwa okwu mkpụrụ ndụ ihe nketa na njikọ protein, na-akwalite mbelata nke ọnwụ na nkwụsịtụ na mmepe nke pathological na ndị agadi [3] . Ugbu a, nyocha nke Epitalon lekwasịrị anya na ọkwa nnwale anụmanụ, na ekpebibeghị ịdị irè ya na nchekwa ogologo oge n'ime mmadụ. Ọ bụ ezie na ụfọdụ ọmụmụ anụmanụ enwetawo ihe na-agba ume, dị ka na òké, Epitalon na-ejikọta ya na ogologo ndụ na ahụike ka mma, ntinye nke nsonaazụ ndị a na ụmụ mmadụ ka na-achọ nyocha ọzọ [1].
Kedu otu esi eme Epitalon na ngalaba mgbochi ịka nká?
Mbelata ọkwa nke ụdị oxygen na-emeghachi omume:
Ụdị oxygen na-emeghachi omume (ROS) na-ekere òkè dị mkpa na usoro ịka nká nke oocytes. Oke ROS ga-eme ka mmebi oxidative na-emebi oocytes, na-emetụta àgwà ha na ikike mmepe ha. Nnyocha e mere egosiwo na Epitalon nwere ike belata ọnụ ọgụgụ nke cytoplasmic nkewa nke oocytes kpatara ịka nká na ọdịnaya nke intracellular reactive oxygen ụdị [2] . Dị ka antioxidant, Epitalon nwere ike wepụ ROS intracellular ma belata mmebi nke oocytes. Kpọmkwem, enwere ike nweta ya n'ụzọ abụọ a: Nke mbụ, na-ekpochapụ ROS ozugbo. Epitalon nwere ike nwee ike imeghachi omume na ROS ozugbo wee gbanwee ya ka ọ bụrụ ihe na-adịghị njọ. Nke abụọ, ịkwalite ọrụ nke enzymes antioxidant. Epitalon nwere ike kpalie ọrụ nke enzymes antioxidant intracellular, dị ka superoxide dismutase (SOD), catalase (CAT), wdg. Enzymes ndị a nwere ike inye aka n'igbu ROS ma nọgide na-enwe nguzozi redox intracellular.
Na-emeziwanye ọrụ mitochondrial:
Mitochondria na-arụ ọrụ dị mkpa na metabolism ike na ndụ cell nke oocytes. Dị ka afọ oocytes, ọrụ mitochondrial ga-eji nwayọọ nwayọọ daa, na-egosipụta dị ka mbelata nke ike nke mitochondrial akpụkpọ anụ na mbelata na nnomi nọmba nke mitochondrial DNA. Epitalon nwere ike ime ka akpụkpọ ahụ mitochondrial dịkwuo elu na ọnụọgụ nke DNA mitochondrial [2] . Nke a na-enyere aka melite ike ọkọnọ nke oocytes na ịnọgide na-enwe nkịtị physiological ọrụ nke mkpụrụ ndụ. Usoro a kapịrị ọnụ nke omume nwere ike ịgụnye: Nke mbụ, ịbawanye ikike nke mitochondrial membrane. Idokwa ike nke akpụkpọ ahụ mitochondrial dị oke mkpa maka ọrụ nkịtị nke mitochondria. Epitalon nwere ike ịbawanye ikike nke mitochondrial site n'ịhazi ọwa ion ma ọ bụ na-ebufe protein na akpụkpọ ahụ mitochondrial, na-eme ka ike mmepụta ike nke mitochondria dịkwuo elu. Nke abụọ, ịba ụba nnomi nke DNA mitochondrial. Ịbawanye nọmba nnomi nke DNA mitochondrial nwere ike melite ikike njikọ nke mitochondria ma nyekwuo ume maka mkpụrụ ndụ. Epitalon nwere ike ịbawanye nọmba nnomi nke DNA mitochondrial site n'ịkwalite mmegharị nke DNA mitochondrial ma ọ bụ ibelata mmebi ya.
Mbelata morphology spindle na-adịghị mma na exocytosis na-adịghị mma nke granules cortical:
N'oge usoro ịka nká nke oocytes, oke nke morphology spindle na-adịghị mma na exocytosis na-adịghị mma nke cortical granules ga-abawanye, nke ga-emetụta fatịlaịza na ike mmepe embrayo nke oocytes. Epitalon nwere ike ibelata oke nke morphology spindle na-adịghị mma na exocytosis nke cortical granules [2] . Nke a nwere ike ịbụ n'ihi mmetụta nchịkwa nke Epitalon na nkwụsi ike nke cytoskeleton na akpụkpọ ahụ cell: Nke mbụ, na-eme ka ọkpụkpụ spindle guzosie ike. Spindle bụ ihe dị mkpa na usoro nkewa nke cell, na ọdịdị ọdịdị ya na-adịghị mma ga-eduga na nkewa chromosome na-adịghị mma ma na-emetụta mmepe nke oocytes. Epitalon nwere ike ime ka ihe owuwu spindle kwụsie ike site n'ịhazi polymerization na depolymerization nke tubulin, na-ebelata ihe omume nke morphology na-adịghị mma. Nke abụọ, na-ejigide nkwụsi ike nke granules cortical. Cortical granules na-arụ ọrụ dị mkpa n'ime usoro ọmụmụ nke oocytes. Epitalon nwere ike idowe nkwụsi ike nke granules cortical site n'ịhazi ikike nke akpụkpọ ahụ cell ma ọ bụ akara calcium ion, na-ebelata ihe omume exocytosis na-adịghị mma.
Mbelata akara apoptosis:
N'oge usoro ịka nká nke oocytes, akara apoptosis ga-abawanye, na-eduga na ọnwụ cell. Epitalon nwere ike ibelata ọnụọgụ dị mma nke ntụpọ Annexin V na ike fluorescence nke γH2AX na in vitro agadi oocytes [2] . Nke a na-egosi na Epitalon nwere ike ibelata apoptosis nke oocytes. Usoro a kapịrị ọnụ nwere ike ịgụnye: Nke mbụ, igbochi ụzọ mgbama apoptosis. Epitalon nwere ike igbochi nnyefe nke akara apoptosis site na ịhazi protein ndị bụ isi na ụzọ akara apoptosis, dị ka protein ezinụlọ Bcl-2 na protein ezinụlọ caspase, ma belata ọnwụ cell. Nke abụọ, ịnọgide na-enwe nkwụsi ike genomic. γH2AX bụ otu n'ime akara nke mmebi DNA. Epitalon nwere ike idowe nkwụsi ike genomic site na ibelata mmebi DNA na ibelata akara apoptosis.
Epitalon kwadoro iguzosi ike n'ezi ihe na nkesa CG.
Isi mmalite: PubMed [2]
Kedu otu esi eme Epitalon na ọgwụgwọ nke ọrịa neurodegenerative?
Iwu nke ọrụ mgbochi:
Nnyocha egosiwo na Epitalon nwere ike imetụta nzaghachi mgbochi nke ụmụ oke n'okpuru ọnọdụ nrụgide dị iche iche. N'ihu nrụgide ntụgharị ntụgharị na-akpali akpali na mgbochi immunosuppressive jikọtara ọnụ, Epitalon nwere ike ịbawanye ọrụ mmụba nke thymocytes [4] . Nke a pụtara na Epitalon nwere ike ịkwalite nguzogide ahụ na ọrịa neurodegenerative site na ịhazi usoro ahụ ji alụso ọrịa ọgụ. Mgbasa nke thymocytes nwere njikọ chiri anya na ọrụ nke usoro ahụ ji alụso ọrịa ọgụ, usoro ahụ ji alụso ọrịa ọgụ na-ekerekwa òkè dị mkpa na omume na mmepe nke ọrịa neurodegenerative. Dịka ọmụmaatụ, ụfọdụ ọrịa neurodegenerative nwere ike jikọta ya na arụ ọrụ na-adịghị mma ma ọ bụ arụ ọrụ nke usoro ahụ ji alụso ọrịa ọgụ. Mmetụta na-akwalite Epitalon na mmụba nke thymocytes nwere ike inye aka ịnọgide na-enwe nguzozi nke usoro ahụ ji alụso ọrịa ọgụ, si otú a na-ebelata mgbaàmà nke ọrịa neurodegenerative.
Mmetụta na ụzọ ntụgharị mgbaàmà:
Epitalon nwere mmetụta nchịkwa na interleukin-1β (IL-1β) ụzọ ntụgharị mgbaàmà. Kpọmkwem, Epitalon nwere ike ịbawanye mmetụta synergistic nke IL-1β ma na-emetụta ọrụ nke isi enzyme na ụzọ transduction signal ceramide na cerebral cortex membrane, ya bụ akpụkpọ anụ na-anọpụ iche sphingomyelinase (nSMase) [4] . IL-1β bụ cytokine dị mkpa na-etinye aka n'ọtụtụ usoro physiological na pathological. Na ọrịa neurodegenerative, okwu na-adịghị mma nke IL-1β nwere ike iduga neuroinflammation na mmebi neuronal. Site n'ịhazi ụzọ ntụgharị mgbaàmà IL-1β, Epitalon nwere ike ibelata neuroinflammation ma chebe neurons site na mmebi. Na mgbakwunye, mgbanwe na ọrụ nke nSMase na-emetụtakwa ọrịa neurodegenerative. Usoro nke ọrụ nke nSMase site na Epitalon nwere ike inye aka ịnọgide na-arụ ọrụ nkịtị nke mkpụrụ ndụ akwara. Na njedebe, usoro nke Epitalon na-agwọ ọrịa ọrịa neurodegenerative nwere ike ịgụnye nhazi usoro mgbochi na nhazi nke ụzọ ntụgharị mgbaàmà. Otú ọ dị, nnyocha e mere ugbu a na Epitalon na ọgwụgwọ nke ọrịa neurodegenerative ka dị na mbido mbụ, a chọkwara nyocha ọzọ iji gosi na ọ dị irè na nchekwa ya.
Ọganihu nyocha nke Epitalon
Mmetụta na àgwà nke oocytes
Na-egbu oge ịka nká nke oocytes:
In vitro nnwale ọmụmụ achọpụtala na Epitalon nwere ike ibelata ọkwa nke intracellular reactive oxygen ụdị (ROS) na agadi òké oocytes mgbe ovulation. Ka oge na-aga, ikike mmepe nke oocytes ga-eji nwayọọ nwayọọ na-ebelata ka ovulation na vivo ma ọ bụ in vitro. Dị ka peptide dị mkpụmkpụ sịntetik, Epitalon na-eme otu ihe ahụ na melatonin ma bụrụ antioxidant dị irè, nke nwere ike ịba uru nke ịgbatị ndụ. Ọgwụgwọ na Epitalon belatara ugboro ole ntụpọ spindle na nkesa na-adịghị mma nke cortical granules n'ime awa 12 na awa 24 nke ịka nká, n'otu oge ahụ na-abawanye ikike nke mitochondrial na mkpụrụ nke mitochondrial DNA, si otú ahụ belata apoptosis nke oocytes n'ime awa 24 nke ịka nká in vitro. Nsonaazụ ndị a na-egosi na Epitalon nwere ike igbu oge usoro ịka nká nke oocytes in vitro site na ịhazi ọrụ mitochondrial na ọkwa ROS [2].
Ịkwalite ogo nke oocytes:
Ịgbakwunye 0.1 mM nke Epitalon na usoro omenala in vitro nwere ike ibelata ọnụego cytoplasmic nkewa na parthenogenetic activation nke oocytes kpatara site na in vitro ịka nká mgbe ovulation gasịrị, belata oke nke morphology spindle na-adịghị mma na exocytosis na-adịghị ahụkebe nke cortical granules, na-abawanye mitochondrial akpụkpọ anụ na mitochondrial ọnụ ọgụgụ DNA dị mma, na-ebelata ọnụ ọgụgụ mitochondrial nke ọma na DNA. Annexin V ntụpọ na fluorescence ike nke γH2AX in vitro agadi oocytes. Nke a na-egosi na Epitalon nwere ike imeziwanye nsogbu nke organelles n'oge usoro ịka nká in vitro nke oocytes ma melite ogo oocytes (Xue Yue).
Mmetụta dị na ọdịiche nke mkpụrụ ndụ akwara
Nnyocha achọpụtala na AEDG peptide (Epitalon) nwere ike ịbawanye njikọ nke ihe nrịbama dị iche iche nke neurogenic na gingival mesenchymal stem cell, dị ka Nestin, GAP43, β Tubulin III, na Doublecortin. Usoro ihe nlegharị anya nke mkpụrụ ndụ na-egosi na Epitalon na-ejikọta ya na H1/6 na H1/3 histones, nke nwere ike ịbụ otu n'ime usoro maka ịbawanye nsụgharị nke mkpụrụ ndụ ihe nketa neuronal ndị a [5].
Mmetụta nchịkwa na usoro ụjọ ahụ
Na-achịkwa ọrụ neuronal:
Site na nyocha banyere oke, achọpụtara na intranasal infusion nke Epitalon (2 ng) nwere ike mee ka ọrụ akwara nke ụbụrụ ụbụrụ nke oke dị n'ime nkeji ole na ole n'ime nkeji ole na ole, na ọkụ ọkụ nke neurons na-abawanye site na 2-2.5 ugboro [6] . N'ime ndekọ ụfọdụ, a hụkwara nzaghachi dị mgbagwoju anya nwere usoro dị iche iche. Mmụba nke ọrụ neurons site na Epitalon na-ebute site na ọnụọgụ dị elu nke nkeji na-arụ ọrụ na nsonye nke sel ndị gbachiri nkịtị. Ọ dịkarịa ala, ọkwa mbụ nke Epitalon nwere ike ịkọwa site na mmetụta kpọmkwem nke peptide a na sel nke cortex moto.
Mmetụta nchebe nrụgide:
Epitalon nwere mmetụta nchebe nrụgide na ụmụ oke ndị ekpughere n'ọnọdụ nrụgide dị iche iche. Nnwale egosila na Epitalon na-abawanye ọrụ mmụba nke thymocytes. Ma ọ na-emewanyewanye n'okpuru nrụgide ntụgharị na-akpali akpali ma ọ bụ na-egbochi ya n'okpuru nrụgide jikọtara ọnụ nke immunosuppressive, Epitalon nwere ike ịrụ ọrụ nhazi (Vladimir Kh Khavinson, 2002). N'otu oge ahụ, Epitalon nwekwara ike ịbawanye mmetụta synergistic nke interleukin-1β (IL-1β) ma nwee mmetụta na mgbanwe nke ọrụ sphingomyelinase (nSMase) na akpụkpọ anụ ụbụrụ nke ụbụrụ na-akpata site na nrụgide. Nke a na-egosi na Epitalon nwere mmetụta nchebe nrụgide na ọkwa nke ntụgharị mgbaàmà IL-1β na ụzọ sphingomyelin na n'ogo nke mmụba thymocyte lekwasịrị anya na akwara akwara.
Mmetụta na ọrụ endocrine nke primates na-abụghị mmadụ:
Na enwe rhesus agadi, Epitalon nwere ike ibelata ọkwa basal nke glucose na insulin ma mee ka ọkwa melatonin dị n'abalị. N'otu oge ahụ, Epitalon nwere ike belata mpaghara n'okpuru usoro nzaghachi glucose plasma, mụbaa ọnụ ọgụgụ 'n'efu' nke glucose, ma mee ka usoro insulin plasma na-agbanwe agbanwe na nzaghachi nke nchịkwa glucose. Nke a na-egosi na Epitalon bụ ihe na-ekwe nkwa maka iweghachi ọrụ endocrine metụtara afọ na primates [7].
Enwere ike itinye Epitalon n'ịgwọ ọrịa nke sistem ụjọ
Ọrịa Alzheimer: Ọrịa Alzheimer bụ ọrịa neurodegenerative a na-ahụkarị, nke a na-akọwakarị site na mbelata ọrụ ọgụgụ isi na mwepu ebe nchekwa. Nnyocha e mere ugbu a na-egosi na ọrịa Alzheimer na-emetụta ọdịiche neurogenic na-adịghị mma. Ọnụ ọgụgụ nke mkpụrụ ndụ stem neural na ụbụrụ nke ndị ọrịa Alzheimer na-ebelata, a na-egbochikwa ikike ọdịiche ha. Epitalon nwere ike ịkwalite mmụba na ọdịiche nke mkpụrụ ndụ stem neural, mụbaa ọnụọgụ neurons, ma melite ọrụ ọgụgụ isi nke ndị ọrịa Alzheimer. Na mgbakwunye, Epitalon nwekwara ike ịhazi ntọhapụ nke neurotransmitters, meziwanye ebe nchekwa na ikike mmụta nke ndị ọrịa Alzheimer [8].
Ọrịa Parkinson: Ọrịa Parkinson bụ ọrịa neurodegenerative nke a na-ejikarị na nsogbu moto. Isi ihe kpatara ọrịa ya bụ mfu nke neurons dopaminergic na substantia nigra. Ụzọ ọgwụgwọ dị ugbu a na-akasị ebelata mgbaàmà ahụ site n'ịgbakwụnye dopamine ma ọ bụ igbochi mmebi nke dopamine, mana ụzọ ndị a enweghị ike ịkwụsị ọganihu nke ọrịa ahụ. Mgbanwe mkpụrụ ndụ akwara akwara bụ usoro ọgwụgwọ nwere ike ime, mana isi mmalite na ike dị iche iche nke mkpụrụ ndụ stem neural ka bụ nsogbu. Epitalon nwere ike ịkwalite mmụba na ọdịiche nke mkpụrụ ndụ stem neural, mụbaa ọnụọgụ dopaminergic neurons, ma melite ọrụ moto nke ndị ọrịa ọrịa Parkinson [8].
Ọrịa strok na ụbụrụ: Ọrịa strok bụ ọrịa cerebrovascular na-emekarị, na isi ihe na-esi na ya pụta bụ ọnwụ nke neurons na arụ ọrụ akwara ozi. mmerụ ahụ ụbụrụ nwekwara ike iduga n'iyi nke neurons na arụghị ọrụ. Mkpụrụ ndụ akwara akwara na-arụ ọrụ dị mkpa na nrụzi na mmụghachi mgbe ọrịa strok na ụbụrụ merụrụ ahụ. Epitalon nwere ike ịkwalite mmụba na ọdịiche nke mkpụrụ ndụ sel akwara, mụbaa ọnụọgụ neurons, ma melite ọrụ akwara ozi nke ndị ọrịa strok na ụbụrụ merụrụ ahụ [8].
N'ikpeazụ, dị ka tetrapeptide sịntetik, isi usoro mgbochi ịka nká nke Epitalon dị n'ịgbalite nkwupụta nke telomerase reverse transcriptase subunit (TERT), ịgbatị ogologo telomeres na ịnọgide na-arụ ọrụ telomerase, si otú a na-etinye aka na isi usoro nke ịka nká cell. Ihe ọ pụtara bụ na nhụta mbụ nke mgbochi ịka nká site n'echiche nke telomere bayoloji, na-emebi njedebe nke antioxidants omenala nke na-elekwasị anya naanị free radicals, na inye ihe mgbaru ọsọ ọhụrụ maka igbu oge ọrịa ndị metụtara afọ dịka ọrịa Alzheimer na ọrịa obi. Ọ bụ ezie na nchekwa ya dị ogologo oge (karịsịa ihe ize ndụ nke ọrịa kansa) ka kwesịrị ikwenye na usoro nke atọ nke ụlọ ọgwụ, dị ka nyocha na mmepe mmepe nke mbụ telomerase activator-ụdị ọgwụ mgbochi ịka nká, ọ na-egosi ọganihu mgbanwe na ntinye aka na ịka nká site na mmụba mgbaàmà na nhazi usoro ihe omimi na a na-atụ anya ịkwalite ogologo ndụ ahụike mmadụ.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Akwụkwọ akụkọ sayensị Vladimir Khavinson bụ onye ama ama Russia biogerontologist na onye nyocha bioregulator peptide. Ọ bụ onye isi nke St. Petersburg Institute of Bioregulation na Gerontology na onye so na Russian Academy of Medical Sciences. Khavinson enyela nnukwu onyinye na ngalaba nyocha ịka nká wee depụta ọtụtụ akwụkwọ n'akwụkwọ akụkọ ndị a ma ama dịka 'Molecular Biology of Aging' na 'Journal of Anti-Aging Medicine'. Ọrụ ya na-elekwasị anya na mmepe na ntinye nke peptide bioregulators iji lụso ọrịa ndị metụtara afọ ọgụ na imeziwanye ahụike. Nnyocha Khavinson enweela mmetụta na ngalaba nke gerontology, na-enye nghọta ọhụrụ na ụzọ ọgwụgwọ maka ịka nká. Edepụtara Vladimir Khavinson na ntụaka ntụaka [5].
