title: Intracellular Calcium Plays a Critical Role in the Microcystin-LR-Elicited Neurotoxicity Through PLC/IP3 Pathway.
abstract: Neurotoxicity of microcystin-leucine-arginine (MCLR) has been widely reported. However, the mechanism is not fully understood. Using primary hippocampal neurons, we tested the hypothesis that MCLR-triggered activation in intracellular free calcium concentration ([Ca(2+)](i)) induces the death of neurons. Microcystin-leucine-arginine inhibited cell viability at a range of 0.1 to 30 μmol/L and caused a dose-dependent increase in [Ca(2+)](i). This increase in [Ca(2+)](i) was observed in Ca(2+)-free media and blocked by an endoplasmic reticulum Ca(2+) pump inhibitor, suggesting intracellular Ca(2+) release. Moreover, pretreatment of hippocampal neurons with intracellular Ca(2+) chelator (O,O'-bis (2-aminophenyl) ethyleneglycol-N,N,N',N'-tetraacetic acid, tetraacetoxy-methyl ester) and inositol 1,4,5-trisphosphate receptor antagonist (2-aminoethoxydiphenyl borate) could block both the Ca(2+) mobilization and the neuronal death following MCLR exposure. In contrast, the ryanodine receptor inhibitor (dantrolene) did not ameliorate the effect of MCLR. In conclusion, MCLR disrupts [Ca(2+)](i) homeostasis in neurons by releasing Ca(2+) from intracellular stores, and this increase in [Ca(2+)](i) may be a key determinant in the mechanism underlying MCLR-induced neurotoxicity.
authors.affiliation: Department of Pharmacology, Hubei University of Science and Technology, Xianning, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Liu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, Hubei, China.
authors.forename: Cairong
authors.initials: C
authors.lastname: Li
authors.affiliation: Fisheries College, Huazhong Agricultural University, Wuhan, China whtjwjh@163.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000187:drug effects; D008297:Male; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR; D002118:Calcium
keywords: calcium imaging; hippocampal neurons; microcystin-LR; neurotoxicity