title: Interleukin-6 reduces NMDA-induced Ca2+ overload via prevention of Ca2+ release from intracellular store.
abstract: A mechanism for neuroprotection of interleukin-6 (IL-6) via reduction of intracellular Ca2+ overload induced by N-methyl-D-aspartate (NMDA) was explored. Cerebellar granule neurons (CGNs) from postnatal 8-day infant rats were chronically exposed to IL-6 for 8 days. Confocal laser scanning microscope was used to measure dynamic changes of intracellular Ca2+ fluorescence intensity. NMDA triggered an acute and sustaining enhancement of intracellular Ca2+ fluorescence intensity in the cultured CGNs, whereas NMDA stimulation of the neurons that had been exposed to IL-6 reduced the intracellular Ca2+ fluorescence intensity relative to that of non-IL-6-pretreated neurons. Ethylene glycol bis(aminoethylether) tetraacetate (EGTA), a chelator of extracellular Ca2+, decreased the intracellular Ca2+ overload triggered by NMDA. The component of intracellular Ca2+ overload after EGTA treatment was prevented by IL-6 chronic exposure. Cotreatment with dantrolene sodium (DAN) and 2-aminoethoxydiphenylborate (2-APB), blockers of ryanodine receptor (RyR) and inositol 1,4,5-trisphosphate receptor (IP3R), respectively, also decreased the intracellular Ca2+ overload triggered by NMDA. However, the component of intracellular Ca2+ overload after DAN and 2-APB treatment was only slightly but not significantly diminished by IL-6. These results suggest that IL-6 has a neuroprotective effect against NMDA-induced intracellular Ca2+ overload, and that the effect is implemented primarily via a suppression of Ca2+ release from the intracellular Ca2+ store.
authors.affiliation: Department of Physiology, School of Medicine, Nantong University, Nantong, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Sun
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Wang
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Peng
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D009287:Naphthyridines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D014966:Xanthenes / Q000378:metabolism
chemical_list: C516002:2,7-diamido-1,8-naphthyridine; D000814:Aniline Compounds; D001896:Boron Compounds; D002614:Chelating Agents; D015850:Interleukin-6; D009287:Naphthyridines; D014966:Xanthenes; C059715:Fluo-3; D018698:Glutamic Acid; D004533:Egtazic Acid; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium