Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis

J Neural Transm (Vienna). 2016 May;123(5):491-4. doi: 10.1007/s00702-016-1531-8. Epub 2016 Mar 2.

Abstract

Rasagiline, a neuroprotective inhibitor of type B monoamine oxidase, prevented PK111195-induced apoptosis in SH-SY5Y cells through inhibition of mitochondrial apoptosis signaling (J Neural Transm 120:1539-1551, 2013, J Neural Transm 122:1399-1407, 2015). This paper presents that PK11195 induced superoxide flashes, the transit production burst, mediated by cyclosporine A-sensitive membrane permeability transition. Rasagiline prevented superoxide flashes, calcium efflux, and cell death by PK11195. Regulation of the initial pore formation at the inner mitochondrial membrane was confirmed as the decisive mechanism of neuroprotection by rasagiline.

Keywords: Mitochondrial permeability transition; Neuroprotection; Rasagiline; Superoxide flashes.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Cell Line, Tumor
  • Cyclosporine / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indans / pharmacology*
  • Isoquinolines / pharmacology*
  • Mitochondrial Membranes / drug effects*
  • Neuroblastoma / pathology
  • Neuroprotective Agents / pharmacology*
  • Oxygen / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reaction Time / drug effects
  • Selegiline / pharmacology
  • Signal Transduction / drug effects
  • Superoxides / metabolism*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Indans
  • Isoquinolines
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • rasagiline
  • Superoxides
  • Selegiline
  • Cyclosporine
  • Oxygen
  • Calcium
  • PK 11195