Apoptotic Mechanisms Increased by GluT Inhibitor DL-TBOA following Brain Cellular Damage
Keywords:
Glutamate transporter, Glutamate, Apoptosis, Molecular mechanisms, excitotoxicityAbstract
Damage to CNS elements is caused by many neurologic diseases including cerebral palsy and multiple sclerosis, and has been attributed to dyshomeostasis of glutamate signalling. However, molecular mechanism remains elusive. This study was undertaken to elucidate the molecular role of glutamate transporter (GluT) signalling on injury mediated cellular damage using ex-vivo model of brain cultures. Cell injury was induced by transient deprivation of oxygen and glucose. Pharmacological inhibition of GluTs with DL-TBOA was initiated immediately after the end of cell injury. In this study, we detected cell mortality and apoptosis. Caspases, BCL-2 and BDNF transcripts were determined by Q-RT-PCR. Proliferation was detected by replicating cell DNA assay. GluT inhibition following injury was found to result in a further cellular damage as judged by ~ a 58% reduction in cell survival as well as ~ a 29% increase in apoptosis. There was an upregulation of caspase-1,-3,-8 and -9 transcripts. There was also further downregulation of BCL-2 and BDNF transcripts. In addition, there seemed to be proliferative cells increased significantly during the recovery phase. Our study shows that GluTsignalling inhibition enhances cell death by a mechanism involving elaborating pro-death caspases or by suppressing anti-apoptotic BCL-2 and BDNF.
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