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Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria

  • Translational Neurosciences - Original Article
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Abstract

Rasagiline protects neuronal cells from cell death caused by various lines of insults. Its neuroprotective function is due to suppression of mitochondrial apoptosis signaling and induction of neuroprotective genes, including Bcl-2 and neurotrophic factors. Rasagiline inhibits the mitochondrial membrane permeabilization, an initial stage in apoptosis, but the mechanism has been elusive. In this paper, it was investigated how rasagiline regulates mitochondrial death cascade in apoptosis induced in SH-SY5Y cells by PK11195, a ligand of the outer membrane translocator protein of 18 kDa. Rasagiline prevented release of cytochrome c (Cyt-c), and the following caspase 3 activation, ATP depletion and apoptosis, but did not inhibit the mitochondrial membrane potential collapse, in contrast to Bcl-2 overexpression. Rasagiline stabilized the mitochondrial contact site and suppressed Cyt-c release into cytoplasm, which should be the critical point for the regulation of apoptosis. Monoamine oxidase was not associated with anti-apoptotic activity of rasagiline in PK11195-induced apoptosis.

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Abbreviations

ANT:

Adenine nucleotide translocator

CysA:

Cyclosporin A

Cyt-c:

Cytochrome c

∆Ψm:

Mitochondrial membrane potential

FACS:

Fluorescence-augmented flow cytometry

MAC:

Mitochondrial apoptosis induced channel

MAO-A and MAO-B:

Type A and B monoamine oxidase

MMP:

Mitochondrial permeability permeabilization

mPTP:

Mitochondrial permeability transition pore

TSPO:

Outer membrane translocator protein of 18 kDa

VDAC:

Voltage-dependent anion channel

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Acknowledgments

This work was supported by the Research Grant for Longevity Sciences (21A-13) from the Ministry of Health, Labour and Welfare, Japan (W. M and M. N), and the Promotion of Fundamental Studies in Health Sciences of National Institute of Biomedical Innovation, Japan (W. M).

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  1. Makoto Naoi

    Present address: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan

Authors and Affiliations

  1. Department of Neurosciences, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan

    Makoto Naoi & Hong Yi

  2. Department of Cognitive Brain Science, National Research Center for Geriatrics and Gerontology, Obu, Aichi, Japan

    Wakako Maruyama

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  1. Makoto Naoi
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Correspondence to Makoto Naoi.

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Naoi, M., Maruyama, W. & Yi, H. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm 120, 1539–1551 (2013). https://doi.org/10.1007/s00702-013-1033-x

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