Beta-arrestin1 and 2 differently modulate metabotropic glutamate receptor 7 signaling in rat developmental sevoflurane-induced neuronal apoptosis. (28th January 2016)

• Record Type: Journal Article
• Authors: Wang, W.-Y.; Wu, X.-M.; Jia, L.-J.; Zhang, H.-H.; Cai, F.; Mao, H.; Xu, W.-C.; Chen, L.; Zhang, J.; Hu, S.-F.
• Is Part Of: Neuroscience. Volume 313(2016)
• Page Start: 199
• Page End: 212
• Publication Date: 2016-01-28
• Subjects: AMN082 N, N′-bis(diphenylmethyl)-1, 2-ethanediamine dihydrochloride -- CBP CREB binding protein -- CNS central nervous system -- CREB cyclic adenosine 3′, 5′-monophosphate response element binding protein -- Curcumin diferuloylmethane -- DIV days in vitro -- ERK1/2 extracellular signal-regulated kinase 1 and 2 -- FCM flow cytometry -- GPCRs G protein-coupled receptors -- HATs histone acetyltransferases -- HDACs histone deacetylases -- l-AP4 l-2-amino-4-phosphonobutanoate -- LDH lactate dehydrogenase -- MAPK mitogen-activated protein kinase -- mGluRs metabotropic glutamate receptors -- MMPIP 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4, 5-c]pyridin-4(5H)-onehydrochloride -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- MWM Morris water maze -- NMDA N-methyl-d-aspartate -- PND postnatal day -- siRNA small interfering RNA -- TSA trichostatin A -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling -- U0126 1, 4-diamino-2, 3-dicyano-1, 4-bis[2-aminophenylthio]butadiene; mGluR7 -- β-arrestins -- sevoflurane -- apoptosis -- ERK1/2 -- developing brain; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.11.038
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Sevoflurane-induced neuronal apoptosis could be attenuated by mGluR7 activator LAP4 or AMN082. β-Arr2-dependent Phospho-ERK1/2 reduces sevoflurane neurotoxicity by inhibiting Phospho-Bad. β-Arr1 modulates mGluR7 signaling by interacting with CBP and p300 in sevoflurane neurotoxicity. LAP4 or AMN082 improves postnatal sevoflurane-induced emotional and spatial cognitive deficits. Abstract: 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, N′-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).