title: Effect of heat stress and bezafibrate on mitochondrial beta-oxidation: comparison between cultured cells from normal and mitochondrial fatty acid oxidation disorder children using in vitro probe acylcarnitine profiling assay.
abstract: Hyperpyrexia occasionally triggers acute life-threatening encephalopathy-like illnesses, including influenza-associated encephalopathy (IAE) in childhood, and can be responsible for impaired fatty acid beta-oxidation (FAO). In this regard, patients with impaired FAO may be more susceptible to febrile episodes. The effects of heat stress and a hypolipidemic drug, bezafibrate, on mitochondrial FAO were investigated using cultured cells from children with FAO disorders and from normal controls, using an in vitro probe acylcarnitine (AC) profiling assay. Fibroblasts were incubated in medium loaded with unlabelled palmitic acid for 96 h at 37 and 41 degrees C, with or without bezafibrate. AC profiles in culture medium were analyzed by electrospray ionization tandem mass spectrometry. Heat stress, introduced by 41 degrees C, significantly increased acetylcarnitine (C2) but slightly decreased the other acylcarnitines (ACs) in controls and medium-chain acyl-CoA dehydrogenase (MCAD)-deficient cells. On the other hand, in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient cells, accumulation of long-chain ACs were enhanced at 41 degrees C, compared with that at 37 degrees C. In contrast, bezafibrate decreased long-chain ACs with significant increase of C2 in both control and VLCAD-deficient cells at 37 degrees C. These data suggest that heat stress specifically inhibits long-chain FAO, whereas bezafibrate recovers the impaired FAO. Our approach is a simple and promising strategy to evaluate the effects of heat stress or therapeutic drugs on mitochondrial FAO.
authors: Department of Pediatrics, Shimane University School of Medicine, Izumo, Shimane, Japan.
authors: Hong
authors: H
authors: Li
authors: Seiji
authors: S
authors: Fukuda
authors: Yuki
authors: Y
authors: Hasegawa
authors: Hironori
authors: H
authors: Kobayashi
authors: Jamiyan
authors: J
authors: Purevsuren
authors: Yuichi
authors: Y
authors: Mushimoto
authors: Seiji
authors: S
authors: Yamaguchi
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency; D001629:Bezafibrate / Q000494:pharmacology*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013312:Stress, Physiological
chemical_list: D005227:Fatty Acids; D000960:Hypolipidemic Agents; C116917:acylcarnitine; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002331:Carnitine; D001629:Bezafibrate