Acetyl-L-carnitine suppresses apoptosis of thioredoxin 2-deficient DT40 cells

Archives of Biochemistry and Biophysics
Xiaoping ZhuMasayasu Inoue

Abstract

To elucidate the mechanism by which L-carnitine and related metabolites inhibited mitochondria-dependent apoptosis, we used conditional TRX2-knockout DT40 cells (TRX2(-/-)) and compared the properties of signaling pathways leading to apoptosis in the wild and TRX2(-/-) cells. Caspase-3 and 9, but not caspase-8, were strongly activated in TRX2(-/-) cells but not in wild cells. TRX2(-/-) cells generated large amounts of reactive oxygen species that markedly decreased cellular glutathione levels both in cytosol and mitochondria. We found that the critical thiol groups of adenine nucleotide translocator (ANT) were oxidized more easily in TRX2(-/-) cells than in wild cells and that the reduced form, but not oxidized form, of ANT selectively bound to TRX2. Cytochrome c and SOD1 were released from mitochondria more easily in TRX2(-/-) cells than in wild cells. All these phenomena observed with TRX2(-/-) cells were effectively inhibited by acetyl-L-carntine but not L-carnitine. Thus, acetyl-L-carnitine effectively suppressed the oxidative stress in and around mitochondria thereby preventing mitochondrial signaling pathway leading to apoptosis.

References

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Citations

Aug 12, 2009·Journal of Plastic, Reconstructive & Aesthetic Surgery : JPRAS·Andrew D H WilsonGiorgio Terenghi
Jan 1, 2009·Drug Discovery Today. Disease Mechanisms·Shruti Sharma, Stephen M Black
Dec 23, 2009·The Biochemical Journal·Andrew G CoxMark B Hampton
Feb 8, 2011·Free Radical Biology & Medicine·Johanna EngelhardTobias P Dick
Nov 24, 2011·Biochimica Et Biophysica Acta·Vittorio CalabreseEdward J Calabrese
Feb 23, 2021·Toxicology Research·Osama Fouad Ahmed EbrahimLamiaa Mohamed Shawky

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