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 language | English |
|---|---|
| Pages (from-to) | 903-913 |
| Number of pages | 11 |
| Journal | Journal of Applied Toxicology |
| Volume | 34 |
| Issue number | 8 |
| DOIs | |
| State | Published - 1 Jan 2014 |
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Keywords
- Bioenergetics
- Cadmium
- Glycolysis
- HT-22
- Mitochondria
- Pyruvate
Cite this
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In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells. / Poteet, Ethan; Winters, Ali; Xie, Luokun; Ryou, Myoung Gwi; Liu, Ran; Yang, Shaohua.
In: Journal of Applied Toxicology, Vol. 34, No. 8, 01.01.2014, p. 903-913.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - In vitro protection by pyruvate against cadmium-induced cytotoxicity in hippocampal HT-22 cells
AU - Poteet, Ethan
AU - Winters, Ali
AU - Xie, Luokun
AU - Ryou, Myoung Gwi
AU - Liu, Ran
AU - Yang, Shaohua
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Bioenergetics
KW - Cadmium
KW - Glycolysis
KW - HT-22
KW - Mitochondria
KW - Pyruvate
UR - http://www.scopus.com/inward/record.url?scp=84903198386&partnerID=8YFLogxK
U2 - 10.1002/jat.2913
DO - 10.1002/jat.2913
M3 - Article
VL - 34
SP - 903
EP - 913
JO - Journal of Applied Toxicology
JF - Journal of Applied Toxicology
SN - 0260-437X
IS - 8
ER -