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Toxicol Lett. 2011 Jun 24;203(3):219-26. doi: 10.1016/j.toxlet.2011.03.019. Epub 2011 Mar 23.

The disruption of L-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocytic and hepatic cells.

Author information

1
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E2C6, Canada.

Abstract

L-Carnitine is a critical metabolite indispensable for the metabolism of lipids as it facilitates fatty acid transport into the mitochondrion where β-oxidation occurs. Human astrocytes (CCF-STTG1 cells) and hepatocytes (HepG2 cells) exposed to aluminum (Al) and hydrogen peroxide (H₂O₂), were characterized with lower levels of L-carnitine, diminished β-oxidation, and increased lipid accumulation compared to the controls. γ-Butyrobetainealdehyde dehydrogenase (BADH) and butyrobetaine dioxygenase (BBDOX), two key enzymes mediating the biogenesis of L-carnitine, were sharply reduced during Al and H₂O₂ challenge. Exposure of the Al and H₂O₂-treated cells to α-ketoglutarate (KG), led to the recovery of L-carnitine production with the concomitant reduction in ROS levels. It appears that the channeling of KG to combat oxidative stress results in decreased L-carnitine synthesis, an event that contributes to the dyslipidemia observed during Al and H₂O₂ insults in these mammalian cells. Hence, KG may help alleviate pathological conditions induced by oxidative stress.

PMID:
21439360
DOI:
10.1016/j.toxlet.2011.03.019
[Indexed for MEDLINE]

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