Journal of Biochemical and Molecular Toxicology

Volume 20, Issue 4 p. 198-208

Research Article

Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes

Ryan J. Mailloux,

Ryan J. Mailloux

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

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Robert Hamel,

Robert Hamel

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

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Vasu D. Appanna,

Corresponding Author

Vasu D. Appanna

[email protected]

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6Search for more papers by this author

Ryan J. Mailloux,

Ryan J. Mailloux

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

Search for more papers by this author

Robert Hamel,

Robert Hamel

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

Search for more papers by this author

Vasu D. Appanna,

Corresponding Author

Vasu D. Appanna

[email protected]

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6

Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada, P3E 2C6Search for more papers by this author

First published: 11 August 2006

https://doi.org/10.1002/jbt.20137

Citations: 72

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Abstract

Aluminum (Al), a known environmental toxicant, has been linked to a variety of pathological conditions such as dialysis dementia, osteomalacia, Alzheimer's disease, and Parkinson's disease. However, its precise role in the pathogenesis of these disorders is not fully understood. Using hepatocytes as a model system, we have probed the impact of this trivalent metal on the aerobic energy-generating machinery. Here we show that Al-exposed hepatocytes were characterized by lipid and protein oxidation and a dysfunctional tricarboxylic acid (TCA) cycle. BN-PAGE, SDS-PAGE, and Western blot analyses revealed a marked decrease in activity and expression of succinate dehydrogenase (SDH), α-ketoglutarate dehydrogenase (KGDH), isocitrate dehydrogenase-NAD⁺ (IDH), fumarase (FUM), aconitase (ACN), and cytochrome c oxidase (Cyt C Ox). ¹³C-NMR and HPLC studies further confirmed the disparate metabolism operative in control and Al-stressed cells and provided evidence for the accumulation of succinate in the latter cultures. In conclusion, these results suggest that Al toxicity promotes a dysfunctional TCA cycle and impedes ATP production, events that may contribute to various Al-induced abnormalities. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:198–208, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20137

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Volume20, Issue4

August 2006

Pages 198-208

Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes

Abstract

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Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes

Abstract

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