In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells

Ethan Poteet, Ali Winters, Luokun Xie, Myoung Gwi Ryou, Ran Liu, Shaohua Yang

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)903-913
Number of pages11
JournalJournal of Applied Toxicology
Volume34
Issue number8
DOIs
StatePublished - 1 Jan 2014

Keywords

  • Bioenergetics
  • Cadmium
  • Glycolysis
  • HT-22
  • Mitochondria
  • Pyruvate

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