کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6271402 | 1614763 | 2016 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis
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کلمات کلیدی
NMDA1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadieneTerminal deoxynucleotidyl transferase-mediated dUTP nick-end-labelingl-AP4Diferuloylmethaneβ-arrestinsMMPIPAMN082mGluR7U0126mGluRsCBPMWMN-methyl-d-aspartateCREBGPCRsFCMHDACsPNDTSASevoflurane - سووفلوران3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyl tetrazolium bromideERK1/2 - ERK1 / 2G protein-coupled receptors - G گیرنده های پروتئینی همراهMAPK - MAPKMTT - MTTSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNATrichostatin A - تریکوستاتین ADeveloping brain - توسعه مغزTUNEL - تونلApoptosis - خزان یاختهایCNS - دستگاه عصبی مرکزیDIV - دیوdays in vitro - روز in vitropostnatal day - روز پس از زایمانcentral nervous system - سیستم عصبی مرکزیFlow cytometry - فلوسیتومتریlactate dehydrogenase - لاکتات دهیدروژناز LDH - لاکتات دهیدروژناز به صورت مختصر شده LDH Morris water maze - ماز آب آب موریسhistone deacetylases - هیستون deacetylaseshistone acetyltransferases - هیستون استیل ترانسفرازCREB binding protein - پروتئین اتصال CREBmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenHATs - کلاهCurcumin - کورکومینextracellular signal-regulated kinase 1 and 2 - کیناز 1 و 2 تنظیم شده با سیگنال خارج سلولیMetabotropic glutamate receptors - گیرنده های متابوتروپیک گلوتامات
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Beta-arrestins (β-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that β-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. In the present study, we showed that activation of mGluR7 with a group III mGluRs orthosteric agonist LAP4 or an atypical mGluR7 allosteric agonist N,Nâ²-bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) significantly attenuated sevoflurane-induced neuronal apoptosis. Interestingly, this neuroprotective role of LAP4 could be partially reduced by β-arr1 small interfering RNA (siRNA) or β-arr2 siRNA transfection. In contrast, β-arr2 siRNA transfection alone abolished the effects of AMN082 on sevoflurane neurotoxicity. In addition, administration of LAP4 or AMN082 significantly enhanced Phospho-ERK1/2 in sevoflurane neurotoxicity, which could be abrogated by β-arr2 siRNA transfection, but not by β-arr1 siRNA transfection. Increased β-arr2-dependent Phospho-ERK1/2 signaling alleviated sevoflurane neurotoxicity by inhibiting bad phosphorylation. We also found that the neuroprotective role of AMN082 was completely reversed by ERK1/2 inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126). Alternatively, treatment with U0126 partially suppressed the neuroprotective of LAP4, suggesting that other mechanisms may be implicated in this process. Further investigation indicated that, in the scenario of sevoflurane neurotoxicity, application of LAP4 (but not AMN082) increased the interaction of β-arrs with transcriptional factors CREB binding protein (CBP) and p300. LAP4 also enhanced the β-arr1-dependent H3 and H4 acetylation in sevoflurane neurotoxicity. For the behavior study, treatment with LAP4 or AMN082 significantly improved the emotional and spatial learning and memory disorders induced by postnatal sevoflurane exposure. These results suggested that β-arr1 and 2 may differently modulate mGluR7 signaling in developmental sevoflurane neurotoxicity. This study also reveals a β-arr-biased agonism at GPCRs (e.g. mGluR7).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 313, 28 January 2016, Pages 199-212
Journal: Neuroscience - Volume 313, 28 January 2016, Pages 199-212
نویسندگان
W.-Y. Wang, X.-M. Wu, L.-J. Jia, H.-H. Zhang, F. Cai, H. Mao, W.-C. Xu, L. Chen, J. Zhang, S.-F. Hu,