Stimulation of membrane permeability transition by α-lipoic acid and its biochemical characteristics

Sanae Aoyama, Yuya Okimura, Hirofumi Fujita, Eisuke F. Sato, Teruo Umegaki, Koichi Abe, Masayasu Inoue, Kozo Utsumi, Junzo Sasaki

Research output: Contribution to journalArticle

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Abstract

Mitochondria play an important role in apoptosis by generating reactive oxygen species (ROS) and inducing membrane permeability transition (MPT). Recent studies on α-lipoic acid (LA) and its reduced form, dihydrolipoic acid, suggest that these agents (LAs) inhibit apoptosis of cells by means of their antioxidant activity. On the other hand, LAs also stimulate Ca 2+-dependent mitochondrial MPT and induce apoptosis of certain cells. Thus, the role of LAs in apoptotic cell death remains obscure. We investigated the mechanism of LA-induced MPT of mitochondria. Biochemical analysis revealed, in the presence of Ca2+, inorganic phosphate and succinate, LA induced uncoupling of oxidative phosphorylation, stimulated oxidation of pyridine nucleotides and enhanced Ca2+-induced MPT, as characterized by decrease in Ca2+ loading, ROS generation, oxidation of thiol groups of adenine nucleotide translocator, membrane depolarization, swelling, and cytochrome c release in an incubation time and concentration dependent manner. LA also stimulated hydroxyl radical-induced MPT in a α-tocopherol-inhibitable manner. Cyclosporine A, a potent inhibitor of mitochondrial MPT, inhibited all these events induced by LA. These results indicate that, under certain conditions, LA stimulates Ca2+- induced MPT through the decrease in loading capacity of Ca2+ and that MPT is involved in LA-induced apoptotic cell death. Since fairly high doses of LA have been used as a dietary supplement, the possible occurrence of such side effects, including mitochondrial dysfunction and induction of apoptosis in normal tissues, should be studied.

Original languageEnglish
Pages (from-to)1-20
Number of pages20
JournalPhysiological Chemistry and Physics and Medical NMR
Volume38
Issue number1
Publication statusPublished - 2006

Fingerprint

Thioctic Acid
Permeability
Membranes
Apoptosis
Mitochondrial Membranes
Mitochondria
Cell death
Reactive Oxygen Species
Cell Death
Dietary supplements
Tocopherols
Adenine Nucleotides
Oxidative Phosphorylation
Oxidation
Succinic Acid
Dietary Supplements
Cytochromes c
Depolarization
Sulfhydryl Compounds
Hydroxyl Radical

Keywords

  • α-lipoic acid
  • Antioxidant
  • Apoptosis
  • Membrane permeability transition
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Biophysics
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Stimulation of membrane permeability transition by α-lipoic acid and its biochemical characteristics. / Aoyama, Sanae; Okimura, Yuya; Fujita, Hirofumi; Sato, Eisuke F.; Umegaki, Teruo; Abe, Koichi; Inoue, Masayasu; Utsumi, Kozo; Sasaki, Junzo.

In: Physiological Chemistry and Physics and Medical NMR, Vol. 38, No. 1, 2006, p. 1-20.

Research output: Contribution to journalArticle

Aoyama, S, Okimura, Y, Fujita, H, Sato, EF, Umegaki, T, Abe, K, Inoue, M, Utsumi, K & Sasaki, J 2006, 'Stimulation of membrane permeability transition by α-lipoic acid and its biochemical characteristics', Physiological Chemistry and Physics and Medical NMR, vol. 38, no. 1, pp. 1-20.
Aoyama, Sanae ; Okimura, Yuya ; Fujita, Hirofumi ; Sato, Eisuke F. ; Umegaki, Teruo ; Abe, Koichi ; Inoue, Masayasu ; Utsumi, Kozo ; Sasaki, Junzo. / Stimulation of membrane permeability transition by α-lipoic acid and its biochemical characteristics. In: Physiological Chemistry and Physics and Medical NMR. 2006 ; Vol. 38, No. 1. pp. 1-20.
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