Nickel inhibits mitochondrial fatty acid oxidation.
Nickel inhibits mitochondrial fatty acid oxidation.
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DOI：
10.1016/j.bbrc.2015.06.017
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发表时间：
2015-08-07
影响因子：
3.1
通讯作者：
Goetzman, Eric S.
中科院分区：
文献类型：
--
作者：
Uppala, Radha;McKinney, Richard W.;Brant, Kelly A.;Fabisiak, James P.;Goetzman, Eric S.
关键词：
Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis.
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影响因子：
1.6
作者：
Sohn, E. J.;Kim, J.;Kang, D. M.
通讯作者：
Kang, D. M.
影响因子：
3.7
作者：
de Moura MB;Uppala R;Zhang Y;Van Houten B;Goetzman ES
通讯作者：
Goetzman ES
影响因子：
3.2
作者：
Chen, Haobin;Costa, Max
通讯作者：
Costa, Max
影响因子：
6.9
作者：
Goetzman, Eric S.
通讯作者：
Goetzman, Eric S.
DOI：
10.3390/ijerph110100202
发表时间：
2014-01-01
影响因子：
--
作者：
Caruso, Rosalie V.;O'Connor, Richard J.;Fong, Geoffrey T.
通讯作者：
Fong, Geoffrey T.