By Cocer Peptides 
Watanni 1 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
Dubawa
Tsufa ta salula muhimmin tsari ne na ilimin halitta a cikin halittu masu rai kuma yana da alaƙa ta kut-da-kut da yawancin abubuwan da suka shafi ilimin halittar jiki da na cututtuka. Yayin da shekaru ke ƙaruwa, tsufa na salula a hankali yana taruwa, yana haifar da raguwar nama da aikin gabobin jiki da kuma haifar da cututtuka daban-daban da suka shafi shekaru. Peptides, a matsayin wani nau'i na mahimman kwayoyin halittu masu rai, sun sami kulawa mai mahimmanci a fagen binciken tsufa na salula a cikin 'yan shekarun nan. Bincike ya nuna cewa peptides suna taka muhimmiyar rawa wajen daidaita tsarin tsufa na salula. Binciken alakar da ke tsakanin peptides da tsufa na salula yana da matukar mahimmanci don bayyana hanyoyin da ake amfani da su na tsufa da kuma bunkasa maganin tsufa.
Hoto 1. Hanyoyi na tsarin tsufa na fata. (a) Free radicals da oxidative stress theory. Mitochondria yana samar da ROS ta hanyar oxidative metabolism. ROS mai yawa zai iya lalata tsarin mitochondrial da DNA, yana haifar da raguwa a matakan collagen da karuwa a matakan MMP a cikin fata. ( b ) Ka'idar kumburi. Senescent fibroblasts da keratinocytes suna ɓoye adadi mai yawa na abubuwan da suka shafi sirrin sirri, ciki har da TNF-α, IL-1, IL-6, IFN-γ da MMPs. Waɗannan cytokines masu kumburi suna haifar da haɓakar ƙwayar fata ta hanyar haɓaka samar da ROS da kunna hanyar siginar ATM/p53/p21. ( c ) Ka'idar daukar hoto. Hasken hasken ultraviolet yana haifar da samar da ROS da ɓoyewar MMPs, wanda ke lalata abubuwan matrix na fata na fata kamar collagen. ( d ) Nonenzymatic glycosyl chemistry theory. Glycosylation ba enzymatic ba shine amsawa tsakanin rage rage sukari kyauta da rukunin amino ɗin kyauta na sunadaran, DNA da lipids don samar da AGEs da ROS. Tarin AGEs, tare da ROS, na iya haifar da canje-canje a cikin homeostasis cell da tsarin gina jiki.
Tsufa ta salula
(1) Ra'ayi da Halayen Tsufa na salula
Tsufawar salula tana nufin yanayin kamawar girma da ba za a iya jurewa ba wanda sel ke shiga bayan an sami takamaiman adadin rarrabuwa ko kuma an fallasa su ga takamaiman abubuwan damuwa. Yana nuna jerin halaye na yau da kullun, kamar canje-canje a cikin ilimin halittar jiki, gami da ƙarar ƙarar tantanin halitta, daidaitawa, da vacuolization na cytoplasm; kama sake zagayowar tantanin halitta, tare da sel ba sa yaduwa; da ƙara yawan aiki na β-galactosidase (SA-β-gal) mai haɗin kai, wanda a halin yanzu yana ɗaya daga cikin alamomin da aka fi amfani da su na senescence na salula. Canje-canjen phenotype na sirri, inda sel ke ɓoye cytokines daban-daban, chemokines, da proteases, suna samar da yanayin sirri mai alaƙa da senescence (SASP).
(2) Sakamakon Ciwon Hannun Halitta
Lalacewar nama da aikin gabobin jiki
Kwayoyin su ne ainihin tubalan ginin kyallen takarda da gabobin jiki, kuma jin daɗin salula yana haifar da rauni na nama da aikin gabobin. A cikin nama na fata, fibroblasts senescent yana rage haɗin haɗin collagen da fibers na roba, yana haifar da fata ta rasa elasticity, haɓaka wrinkles, kuma suna da raunin gyarawa. A cikin tsarin zuciya da jijiyoyin jini, sel endothelial na hankali na iya haifar da taurin ganuwar jini da rage elasticity, ƙara haɗarin cututtukan zuciya. A cikin tsarin garkuwar jiki, tsufa na ƙwayoyin rigakafi yana raunana aikin kare lafiyar jiki, yana sa mutane su zama masu saukin kamuwa da kamuwa da cutar da kuma rage amsawar rigakafi ga alluran rigakafi.
Haɗin kai tare da cututtukan da suka shafi shekaru
Ana ɗaukar tsufan salula a matsayin muhimmin abin tuƙi a yawancin cututtukan da suka shafi shekaru. A cikin cututtuka na neurodegenerative irin su cutar Alzheimer da cutar Parkinson, tsufa na neuronal yana da alaƙa da tsarin tafiyar da cututtuka irin su mutuwar neuronal da neuroinflammation. A cikin ciwon sukari, tsufa na ƙwayoyin β pancreatic na iya haifar da rashin isasshen insulin, yana shafar tsarin glucose na jini na yau da kullun. Senescence na tantanin halitta kuma yana da hadaddun alaƙa tare da tumarigenesis da ci gaban ƙari. Senescence na farkon tantanin halitta na iya aiki azaman hanyar hana ƙari, yana hana haɓakar ƙwayoyin da suka lalace mara iyaka. Koyaya, a cikin microenvironment na ƙari, abubuwan SASP da aka ɓoye ta sel masu hankali na iya haɓaka haɓakar ƙwayar ƙwayar cuta, mamayewa, da metastasis.
Peptides
(1) Ma'anar da tsarin peptides
Peptides su ne mahaɗan gajerun sarka waɗanda amino acid ɗin da aka haɗa ta hanyar haɗin peptide. Dangane da adadin ragowar amino acid ɗin da suka ƙunshi, ana iya rarraba su zuwa dipeptides, tripeptides, tetrapeptides, da polypeptides, da sauransu. Polypeptides sun fi tsayi, ci gaba, da sarƙoƙin peptide marasa rassa. Yawanci, sarƙoƙin peptide waɗanda ba su wuce 50 amino acid ba ana rarraba su azaman peptides don bambanta su da sunadaran. Duk sarƙar peptide, ban da peptides na cyclic, suna da N-terminal (amino-terminal) da ragowar C-terminal (carboxy-terminal).
(2) Rarraba Peptides
Rarraba ta Source
Endogenous peptides: hada da kwayoyin da kanta da kuma yin daban-daban physiological ayyuka a cikin jiki. Neuropeptides, wanda ke shiga cikin watsa sigina da ka'idoji a cikin tsarin mai juyayi, ciki har da endorphins da enkephalins, waɗanda ke da tasirin analgesic da yanayin yanayi; peptides na hormone, kamar insulin, waɗanda ke da mahimmanci don daidaita ma'aunin sukari na jini.
Exogenous peptides: samu daga abinci ko wasu waje kafofin. Misali, wasu sunadaran abinci na iya zama hydrolyzed ta hanyar enzymes masu narkewa don samar da peptides bioactive, irin su peptides na madara, waɗanda ke da ayyuka masu yawa na ilimin lissafin jiki, gami da tasirin antioxidant da rigakafi-modulating. Peptides da aka shirya ta hanyar haɗin sinadarai ko fasahar kere-kere su ma suna faɗuwa ƙarƙashin peptides na waje kuma ana amfani da su a cikin haɓakar ƙwayoyi da magungunan asibiti.
Rabewa ta Aiki
Peptides na Antioxidant: Yana iya lalata radicals kyauta a cikin jiki da kuma rage lalacewar sel. Misali, an nuna peptides antioxidant na shinkafa bran don haɓaka ayyukan enzymes antioxidant kamar catalase (CAT) da glutathione peroxidase (GSH-Px) a cikin mitochondria na zuciya da kyallen kwakwalwa na D-galactose-induced tsofaffin beraye, rage matakin mitochondrial DNA shafe maye gurbi a cikin kwakwalwa.
peptides masu daidaita rigakafi: Waɗannan suna daidaita aikin garkuwar jiki, haɓakawa ko danne martanin rigakafi. Wasu peptides da aka samo daga kwayoyin ruwa na iya kunna ƙwayoyin rigakafi, haɓaka ƙarfin kariya na jiki, da kuma taimakawa wajen tsayayya da cututtuka na ƙwayoyin cuta da ci gaban ƙari.
peptides masu haɓaka haɓakar salula: Waɗannan suna tasiri hanyoyin salon salula kamar haɓakawa, bambance-bambance, da apoptosis. Alal misali, haɓakar haɓakar epidermal (EGF) yana haɓaka haɓakawa da bambance-bambancen ƙwayoyin epidermal, yana hanzarta warkar da rauni.
Matsayin peptides a cikin tsufa na salula
(1) Tsarin aikin mitochondrial
Mitochondria yana taka muhimmiyar rawa wajen samar da makamashin salula da kuma watsa sigina, kuma rashin aikinsu yana da alaƙa da tsufa na salula. Mitochondria-derived peptides (MDPs) irin su humanin da MOTS-c suna taka muhimmiyar rawa a cikin tsarin tsufa na salula. Bayan jin daɗi da aka haifar ta hanyar gajiyar kwafi, doxorubicin, ko hydrogen peroxide jiyya a cikin fibroblasts na ɗan adam na farko, lambobin mitochondrial suna ƙaruwa, matakan numfashi na mitochondrial sun tashi, kuma matakan ɗan adam da MOTS-c suma suna haɓaka. Gudanar da humanin da MOTS-c matsakaici yana ƙara yawan numfashi na mitochondrial a cikin doxorubicin-induced senescent sel da kuma wani sashi yana daidaita sassan SASP ta hanyar hanyar JAK, yana nuna cewa MDPs suna taka muhimmiyar rawa a cikin mitochondrial makamashi metabolism da kuma samar da SASP a cikin kwayoyin halitta.
Hoto 2 Mitochondrial taro da makamashi suna canzawa a lokacin da ake haifar da doxorubicin. (A) Mitochondrial DNA (mtDNA) kwafin lamba a cikin marasa hankali (quiescent) da sel masu hankali. (B) Hotunan wakilai na Tom20 (kore; mitochondria) da Hoechst 33258 (blue; nucleus) immunostaining a cikin wadanda ba su da hankali (quiescent) da kwayoyin halitta. Tsawon sikelin, 20 μm. An auna wurin tabon Tom20 a kowane tantanin halitta ta amfani da ImageJ. (C) Matakan ATP na salula a cikin sel marasa hankali (quiescent) da sel masu hankali. (D) Yawan amfani da iskar oxygen ta salula (OCR) a cikin ƙwayoyin da ba su da hankali da jin daɗi. An ƙididdige numfashin basal, ƙarfin numfashi, da samar da ATP dangane da alluran fili na jeri bisa ga umarnin masana'anta. (E) Matsakaicin adadin acidification na extracellular (ECAR) a cikin sel marasa hankali (quiescent) da ƙwayoyin ji.
(2) Tasiri kan hanyoyin sigina masu alaƙa da tsufa
hanyar p53-p21
Sunan furotin p53 shine maɓalli mai daidaita yanayin senescence na salula. Lokacin da aka fallasa ƙwayoyin sel zuwa damuwa irin su lalacewar DNA, p53 an kunna shi, yana haifar da bayyanar p21, wanda ke haifar da sake zagayowar tantanin halitta don kamawa a lokacin G1, wanda ke haifar da yanayin salon salula. Wasu peptides na iya daidaita hanyar p53-p21, ta haka ne ke haifar da ci gaban jin daɗin salula. Wasu ƙananan ƙwayoyin peptides na iya yin hulɗa tare da furotin p53, hana ayyukansa kuma ta haka yana jinkirta jinkirin salon salula. Nazarin ya nuna cewa takamaiman peptides na iya toshe hulɗar tsakanin p53 da MDM2 (sunan furotin da ke daidaita p53 mara kyau), yana daidaita furotin p53 da kuma kiyaye shi a matakin da ya dace don guje wa kunnawa da yawa wanda ke haifar da yanayin salon salula.
Hanyar Rb-E2F
Furotin Rb wani muhimmin furotin ne na tsarin sake zagayowar tantanin halitta wanda ke ɗaure da ma'aunin rubutun E2F don hana bayyanar ƙwayoyin halittar da ke da alaƙa da sake zagayowar tantanin halitta. Lokacin da furotin na Rb ya kasance phosphorylated kuma ba ya aiki, E2F yana fitowa, yana inganta shigarwar tantanin halitta a cikin lokaci S don kwafin DNA. A lokacin tsinkayar salon salula, sauye-sauye a cikin hanyar Rb-E2F suna haifar da kama zagayen tantanin halitta. Wasu peptides na iya daidaita yanayin salon salula ta hanyar daidaita yanayin phosphorylation na furotin Rb ko tasiri ayyukan E2F. Wasu peptides na iya hana Rb protein phosphorylation, kiyaye kwanciyar hankali na Rb-E2F hadaddun kuma ta haka yana jinkirta jinkirin salon salula.
(III) Dokokin SASP
SASP ya ƙunshi cytokines daban-daban, chemokines, da proteases, da sauransu. Sirrin sa ba wai kawai yana rinjayar microenvironment na sel masu hankali da kansu ba amma kuma yana rinjayar kyallen takarda da sel da ke kewaye da su, yana haɓaka martanin kumburi da ƙwayar nama. Wasu peptides na iya daidaita samar da SASP da rage illolin sa. An kuma gano wasu peptides da aka samo daga tsire-tsire don tsara SASP ta hanyar hana kunna takamaiman hanyoyin sigina da rage maganganun abubuwan da ke da alaƙa da SASP.
Aikace-aikace na Peptides a cikin Jinkirin tsufa na salula
(1) Aikace-aikace a cikin Kayan Kula da Fata
Tare da karuwar damuwa na jama'a game da tsufa na fata, peptides sun sami aikace-aikacen tartsatsi a cikin masana'antar fata. Misali, wasu samfuran kula da fata da ke ɗauke da peptides suna da'awar cewa suna da anti-wrinkle da tasirin fata. Bincike ya nuna cewa wasu peptides na iya inganta haɓakar collagen da haɓaka elasticity na fata. Peptides kuma na iya daidaita metabolism na ƙwayoyin fata, haɓaka aikin shingen fata, rage lalacewar ƙwayoyin fata waɗanda abubuwan waje ke haifarwa kamar hasken UV, da rage saurin tsufa na fata.
Hoto na 3 Tsufa daga ƙarami zuwa babba.
(2) Aikace-aikace a Ci gaban Drug
Maganin Cututtukan Neurodegenerative
Ci gaban miyagun ƙwayoyi Peptide yana riƙe da babban alƙawari don magance tsufa na neuronal a cikin cututtukan neurodegenerative. Peptides wanda ke daidaita hanyoyin siginar cikin salula, inganta rayuwar neuronal, da sauƙaƙe gyare-gyare an haɓaka don maganin cutar Alzheimer da cutar Parkinson. Wasu peptides na iya hana haɓakar sunadaran da ba su da kyau a cikin ƙwayoyin cuta, rage kumburin neuron, da jinkirta tsufa na neuronal da mutuwa. Wani peptide mai suna AC-5216 na iya hana haɗuwar sunadaran β-amyloid kuma inganta aikin fahimi a cikin ƙirar ƙirar cutar Alzheimer.
Maganin Cututtukan Zuciya
A cikin maganin cututtuka na zuciya da jijiyoyin jini, magungunan peptide na iya ƙaddamar da matakai na pathological irin su tsufa na endothelial na jijiyoyi da kuma tsufa na myocardial cell. Misali, wasu peptides na vasoactive na iya daidaita sautin jijiyoyin jini da aikin sel na endothelial, inganta yanayin tsufa na ƙwayoyin jijiyoyi, da rage haɗarin cututtukan zuciya. Wasu peptides kuma na iya haɓaka gyare-gyare da sake farfadowa na ƙwayoyin cuta na zuciya, suna ba da damar aikace-aikace a cikin maganin yanayi irin su ciwon zuciya.
Kammalawa
Tsufa ta salula, a matsayin tsarin ilimin halitta mai rikitarwa, yana rinjayar tsarin lafiya da tsufa na jiki. Peptides, a matsayin muhimmin ajin kwayoyin halitta, suna taka rawa iri-iri wajen daidaita tsufan tantanin halitta. Ta hanyar daidaita aikin mitochondrial, shiga tsakani a cikin hanyoyin siginar da ke da alaƙa da tsufa, da daidaita SASP, peptides suna nuna ikon jinkirta tsufa na salula.
Sources
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