title: The role of glutamate release on voltage-dependent anion channels (VDAC)-mediated apoptosis in an eleven vessel occlusion model in rats.
abstract: Voltage-dependent anion channel (VDAC) is the main protein in mitochondria-mediated apoptosis, and the modulation of VDAC may be induced by the excessive release of extracellular glutamate. This study examined the role of glutamate release on VDAC-mediated apoptosis in an eleven vessel occlusion model in rats. Male Sprague-Dawley rats (250-350 g) were used for the 11 vessel occlusion ischemic model, which were induced for a 10-min transient occlusion. During the ischemic and initial reperfusion episode, the real-time monitoring of the extracellular glutamate concentration was measured using an amperometric microdialysis biosensor and the cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry. To confirm neuronal apoptosis, the brains were removed 72 h after ischemia to detect the neuron-specific nuclear protein and pro-apoptotic proteins (cleaved caspase-3, VDAC, p53 and BAX). The changes in the mitochondrial morphology were measured by atomic force microscopy. A decrease in the % of CBF was observed, and an increase in glutamate release was detected after the onset of ischemia, which continued to increase during the ischemic period. A significantly higher level of glutamate release was observed in the ischemia group. The increased glutamate levels in the ischemia group resulted in the activation of VDAC and pro-apoptotic proteins in the hippocampus with morphological alterations to the mitochondria. This study suggests that an increase in glutamate release promotes VDAC-mediated apoptosis in an 11 vessel occlusion ischemic model.
authors.affiliation: Department of Biomedical Engineering, and Healthcare Industry Research Institute, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Eunkuk
authors.initials: E
authors.lastname: Park
authors.forename: Gi-Ja
authors.initials: GJ
authors.lastname: Lee
authors.forename: Samjin
authors.initials: S
authors.lastname: Choi
authors.forename: Seok-Keun
authors.initials: SK
authors.lastname: Choi
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Chae
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.forename: Hun-Kuk
authors.initials: HK
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D015374:Biosensing Techniques; D053148:Caspase 3 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007511:Ischemia; D017078:Laser-Doppler Flowmetry; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D050994:Voltage-Dependent Anion Channels; D051028:bcl-2-Associated X Protein; D018698:Glutamic Acid; D053148:Caspase 3