Stimulation of Ca2+ release from rat liver mitochondria by the dithiol reagent alpha-lipoic acid

Biochemical Pharmacology
M Schweizer, C Richter

Abstract

Rat liver mitochondria contain a Ca(2+)-specific release pathway stimulated by Ca(2+)-dependent hydrolysis of oxidized intramitochondrial pyridine nucleotides to ADP ribose and nicotinamide. We have previously shown that NAD+ hydrolysis and subsequent Ca2+ release are inhibited by cyclosporine A and that they are only possible when some critical thiols are cross-linked or oxidized, e.g. by phenylarsine oxide, gliotoxin, or peroxynitrite. We now report that the antioxidant alpha-lipoic acid stimulates Ca2+ release from intact mitochondria, i.e. with preservation of the mitochondrial membrane potential and without large-amplitude swelling. The release stimulated by alpha-lipoic acid is inhibited by cyclosporine A and is more effective when the pyridine nucleotides are oxidized. The results strongly suggest that alpha-lipoic acid stimulates the Ca(2+)-specific release pathway from intact mitochondria by oxidizing some vicinal thiols, thereby stimulating hydrolysis of oxidized pyridine nucleotides. These observations further corroborate that intact rat liver mitochondria contain a specific Ca2+ release pathway stimulated by modification of vicinal thiols. Prolonged stimulation of Ca2+ release by lipoic acid followed by its re-uptak...Continue Reading

References

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Citations

Jan 2, 2009·In Vitro Cellular & Developmental Biology. Animal·Masao YamasakiKazuo Nishiyama
Jun 23, 1999·Journal of Neuroimmunology·A J Bruce-KellerM P Mattson
Jun 2, 1998·Free Radical Biology & Medicine·J BustamanteB H Rihn
Jun 24, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S H Ki, S G Kim
Apr 5, 2011·Environmental Toxicology·Wen-Hsiung ChanWalter H Chang
Sep 3, 2009·Annals of the New York Academy of Sciences·Sang Yong ChoiHyeyoung Kim
Mar 11, 2000·European Journal of Biochemistry·M Ziegler
Jul 20, 2002·Toxicology and Applied Pharmacology·Hadi MoiniNils-Erik L Saris

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