Bax-regulated mitochondria-mediated apoptosis is responsible for the in vitro ischemia induced neuronal cell death of Sprague Dawley rat

• DOI: 10.1016/j.neulet.2005.06.070
• Publication Date: 2005-08-04T19:54:58Z
• Authors: Chi-Hsin Lin; Yen-Zhen Lu; Fu-Chou Cheng; Lan-Feng Chu; Chi-Mei Hsueh
• Keywords: Protein Synthesis Inhibitors; 0301 basic medicine; Cytochromes c; Apoptosis; Cerebral Infarction; Intracellular Membranes; Brain Ischemia; Membrane Potentials; Mitochondria; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; Protein Transport; 03 medical and health sciences; Proto-Oncogene Proteins c-bcl-2; Caspases; Nerve Degeneration; Animals; Enzyme Inhibitors; Signal Transduction; bcl-2-Associated X Protein

An in vitro ischemia model was used to determine the molecular mechanisms responsible for the ischemia-induced neuronal cell death. Additionally, the neuronal protective mechanisms of anti-apoptotic drugs against ischemia were also evaluated. In this study, the primary neuronal cultures were incubated in an anoxic chamber with 95% of N2 and 5% of CO2 for various times. The death rate, degree of the apoptotic damage, reduction of mitochondrial membrane potential, translocation of Bax, release of cytochrome C and activation of caspase-9 and -3 were determined at each time point. Results showed that a Bax-regulated mitochondria- mediated apoptosis is responsible for the in vitro ischemia-induced neuronal death. Reduction in mitochondrial membrane potential plays no role in triggering this apoptosis. Furthermore, the anti-apoptotic drugs: furosemide (a Bax blocker) and ZVAD-fmk (caspase inhibitor) but not cyclosporine A (a MPT pore blocker), significantly protected the neurons against ischemia-induced damage. This provides an additional consideration in the future selection of new anti-ischemic drugs.