title: Protective action of L-carnitine on cardiac mitochondrial function and structure against fatty acid stress.
abstract: Cardiovascular risks are frequently accompanied by high serum fatty acid levels. Although recent studies have shown that fatty acids affect mitochondrial function and induce cell apoptosis, L-carnitine is essential for the uptake of fatty acids by mitochondria, and may attenuate the mitochondrial dysfunction and apoptosis of cardiocytes. This study aimed to elucidate the activity of L-carnitine in the prevention on fatty acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoyl-CoA-induced mitochondrial respiration that was observed with L-carnitine was inhibited with oligomycin. The palmitoyl-CoA-induced mitochondrial membrane depolarization and swelling were greatly inhibited by the presence of L-carnitine. In ultrastructural observations, terminally swollen and ruptured mitochondria with little or no distinguishable cristae structures were induced by treatment with palmitoyl-CoA. However, the severe morphological damage in cardiac mitochondria was dramatically inhibited by pretreatment with L-carnitine. Treatment with L-carnitine also attenuated 4-hydroxy-L-phenylglycine- and rotenone-induced mitochondrial swelling even when the L-carnitine could not protect against the decrease in oxygen consumption associated with these inhibitors. Furthermore, L-carnitine completely inhibited palmitoyl-CoA-induced cytochrome c release. We concluded that L-carnitine is essential for cardiac mitochondria to attenuate the membrane permeability transition, and to maintain the ultrastructure and membrane stabilization, in the presence of high fatty acid β-oxidation. Consequently, the cells may be protected against apoptosis by L-carnitine through inhibition of the fatty acid-induced cytochrome c release.
authors.affiliation: Department of Cytology and Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Oyanagi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yano
authors.forename: Masataka
authors.initials: M
authors.lastname: Uchida
authors.forename: Kozo
authors.initials: K
authors.lastname: Utsumi
authors.forename: Junzo
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002331:Carnitine / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects*; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D014803:Vitamin B Complex; D010171:Palmitoyl Coenzyme A; D002331:Carnitine