title: N-methyl-D-aspartate receptor and L-type voltage-gated Ca(2+) channel antagonists suppress the release of cytochrome c and the expression of procaspase-3 in rat hippocampus after global brain ischemia.
abstract: Transient global ischemia reportedly results in glutamate receptor stimulation and harmful Ca(2+)-overloading, then activates some proteins involved in cell apoptosis in vivo and in vitro, but underlying mechanisms remain to be elucidated. Here we evaluated the role of N-methyl-D-aspartate (NMDA) receptor antagonist and L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist in mediating the release of cytochrome c and the expression of caspase-3 precursor protein (procaspase-3). Cytochrome c release from mitochondria is a critical step in the cell apoptotic process. We examined whether cytochrome c was translocated from mitochondria to the cytosol by Western blot in rat hippocampus after 15 min global ischemia. Released cytochrome c interacts with apoptotic protease activating factor-1 and caspase-9, both of which play important roles in the cytochrome c-dependent mitochondrial pathway of apoptosis by activating caspase-3. Our studies demonstrated that the inactive precursor and active cleaved subunits of caspase-3 protease increased dramatically with the extent of reperfusion time. Following pretreatment with ketamine (a non-competitive NMDA receptor antagonist) and nifedipine (L-VGCC antagonist), cytosolic cytochrome c and the expression of procaspase-3 dramatically decreased, which might result in less neuron damage after ischemia.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, PR China.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Zhang
authors.forename: Wanhua
authors.initials: W
authors.lastname: Shen
authors.forename: Guangyi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D003574:Cytochrome c Group / Q000037:antagonists & inhibitors*; D003600:Cytosol / Q000201:enzymology; D004594:Electrophysiology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000201:enzymology*; D015640:Ion Channel Gating / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000201:enzymology; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D061945:Caspase Inhibitors; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; C505410:Casp3 protein, rat; D053148:Caspase 3; D009543:Nifedipine