Neuronal preconditioning with the antianginal drug, bepridil

Tamás Gáspár, Béla Kis, James A. Snipes, Gábor Lenzsér, Keita Mayanagi, F. Bari, David W. Busija

Research output: Contribution to journalArticle

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Abstract

It has recently been shown that the antianginal drug bepridil (BEP) activates mitochondrial ATP-sensitive potassium (mitoKATP) channels and thus confers cardioprotection. Our aim was to investigate whether BEP could induce preconditioning in cultured rat cortical neurons. Although BEP depolarized isolated and in situ mitochondria and increased reactive oxygen species generation, no acute protection was observed. However, a 3-day BEP-treatment elicited dose-dependent delayed neuroprotection against 180 min of oxygen-glucose deprivation (cell viability: untreated, 52.5 ± 0.85%; BEP 1 μmol/L, 59.6 ± 1.53%*; BEP 2.5 μmol/L, 71.9 ± 1.23%*; BEP 5 μmol/L, 95.3 ± 0.89%*; mean ± SEM; *p <0.05 vs. untreated) and 60 min of glutamate excitotoxicity (200 μmol/L; cell viability: untreated, 54.1 ± 0.69%; BEP 1 μmol/L, 61.2 ± 1.19%*; BEP 2.5 μmol/L, 78.1 ± 1.67%*; BEP 5 μmol/L, 91.2 ± 1.20%*; mean ± SEM; *p <0.05 vs. untreated), and inhibited the reactive oxygen species surge upon glutamate exposure. The protection was antagonized with co-application of the superoxide dismutase mimetic M40401, but not with reduced glutathione, catalase, or with the mitoKATP blocker 5-hydroxydecanoate. Furthermore, BEP treatment resulted in increased levels of phosphorylated protein kinase C, manganese-dependent superoxide dismutase, glutathione peroxidase, and Bcl-2. Our results indicate that BEP induces delayed neuronal preconditioning which is dependent on superoxide generation but perhaps not on direct mitoKATP activation.

Original languageEnglish
Pages (from-to)595-608
Number of pages14
JournalJournal of Neurochemistry
Volume102
Issue number3
DOIs
Publication statusPublished - Aug 2007

Fingerprint

Bepridil
Pharmaceutical Preparations
Superoxide Dismutase
Glutamic Acid
Reactive Oxygen Species
Cell Survival
Cells
KATP Channels
Scanning electron microscopy
Mitochondria
Manganese
Glutathione Peroxidase
Superoxides
Catalase
Protein Kinase C

Keywords

  • Bcl-2
  • Mitochondria
  • Neuronal culture
  • Neuroprotection
  • Protein kinase C
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Gáspár, T., Kis, B., Snipes, J. A., Lenzsér, G., Mayanagi, K., Bari, F., & Busija, D. W. (2007). Neuronal preconditioning with the antianginal drug, bepridil. Journal of Neurochemistry, 102(3), 595-608. https://doi.org/10.1111/j.1471-4159.2007.04501.x

Neuronal preconditioning with the antianginal drug, bepridil. / Gáspár, Tamás; Kis, Béla; Snipes, James A.; Lenzsér, Gábor; Mayanagi, Keita; Bari, F.; Busija, David W.

In: Journal of Neurochemistry, Vol. 102, No. 3, 08.2007, p. 595-608.

Research output: Contribution to journalArticle

Gáspár, T, Kis, B, Snipes, JA, Lenzsér, G, Mayanagi, K, Bari, F & Busija, DW 2007, 'Neuronal preconditioning with the antianginal drug, bepridil', Journal of Neurochemistry, vol. 102, no. 3, pp. 595-608. https://doi.org/10.1111/j.1471-4159.2007.04501.x
Gáspár, Tamás ; Kis, Béla ; Snipes, James A. ; Lenzsér, Gábor ; Mayanagi, Keita ; Bari, F. ; Busija, David W. / Neuronal preconditioning with the antianginal drug, bepridil. In: Journal of Neurochemistry. 2007 ; Vol. 102, No. 3. pp. 595-608.
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