title: The disruption of L-carnitine metabolism by aluminum toxicity and oxidative stress promotes dyslipidemia in human astrocytic and hepatic cells.
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.
authors: Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E2C6, Canada.
authors: Joseph
authors: J
authors: Lemire
authors: Ryan
authors: R
authors: Mailloux
authors: Rami
authors: R
authors: Darwich
authors: Christopher
authors: C
authors: Auger
authors: Vasu D
authors: VD
authors: Appanna
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D001253:Astrocytes / Q000378:metabolism*; D002331:Carnitine / Q000378:metabolism*; D045744:Cell Line, Tumor; D050171:Dyslipidemias / Q000139:chemically induced*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007656:Ketoglutaric Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050563:gamma-Butyrobetaine Dioxygenase / Q000378:metabolism
chemical_list: D007656:Ketoglutaric Acids; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000535:Aluminum; D050563:gamma-Butyrobetaine Dioxygenase; D002331:Carnitine