title: In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells.
abstract: Cadmium is a toxic metal with no biological function in higher-order mammals. Humans are exposed to cadmium environmental contamination and the mechanism underlying the cadmium's cytotoxicity is unclear. To better understand this mechanism, we employed murine hippocampal HT-22 cells to test the in vitro effects of cadmium toxicity. Our study indicated that cadmium inhibits both mitochondria oxidative phosphorylation and glycolysis. In turn, this causes depolarization of mitochondrial membrane potential, increase of superoxide production and decrease of ATP generation. Furthermore, we demonstrated that the detrimental action of cadmium in bioenergetics could be mitigated by pyruvate, an intermediate metabolic product. Pyruvate decreased superoxide production, maintained mitochondrial membrane potential, restored glycolysis, mitigated the decrease in cellular ATP and attenuated cadmium cytotoxicity. Our study provides the first evidence that pyruvate might offer promising therapy for cadmium poisoning.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Poteet
authors.forename: Ali
authors.initials: A
authors.lastname: Winters
authors.forename: Luokun
authors.initials: L
authors.lastname: Xie
authors.forename: Myoung-Gwi
authors.initials: MG
authors.lastname: Ryou
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019289:Pyruvic Acid / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002104:Cadmium; D013481:Superoxides; D019289:Pyruvic Acid
keywords: Bioenergetics; Cadmium; Glycolysis; HT-22; Mitochondria; Pyruvate