tailieunhanh - Báo cáo khoa học: Calcium, mitochondria and oxidative stress in neuronal pathology Novel aspects of an enduring theme

The interplay among reactive oxygen species (ROS) formation, elevated intracellular calcium concentration and mitochondrial demise is a recurring theme in research focusing on brain pathology, both for acute and chronic neurodegenerative states. However, causality, extent of contribution or the sequence of these events prior to cell death is not yet firmly established. | ềFEBS Journal REVIEW ARTICLE Calcium mitochondria and oxidative stress in neuronal pathology Novel aspects of an enduring theme Christos Chinopoulos and Vera Adam-Vizi Department of MedicalBiochemistry Semmelweis University NeurobiochemicalGroup Hungarian Academy of Sciences Szentagothai Knowledge Center Budapest Hungary Keywords alpha-ketoglutarate dehydrogenase oxidative stress permeability transition pore store-operated Ca2 entry transient receptor potential TRPM2 TRPM7 Correspondence V. Adam-Vizi Semmelweis University Department of Medical Biochemistry Budapest H-1444 PO Box 262 Hungary Fax 36 1 2670031 Tel 36 1 2662773 E-mail av@ Received 18 October 2005 accepted 14 December 2005 doi The interplay among reactive oxygen species ROS formation elevated intracellular calcium concentration and mitochondrial demise is a recurring theme in research focusing on brain pathology both for acute and chronic neurodegenerative states. However causality extent of contribution or the sequence of these events prior to cell death is not yet firmly established. Here we review the role of the alpha-ketoglutarate dehydrogenase complex as a newly identified source of mitochondrial ROS production. Furthermore based on contemporary reports we examine novel concepts as potential mediators of neuronal injury connecting mitochondria increased Ca2 c and ROS7 reactive nitrogen species RNS formation specifically a the possibility that plasmalemmal nonselective cationic channels contribute to the latent Ca2 c rise in the context of glutamate-induced delayed calcium deregulation b the likelihood of the involvement of the channels in the phenomenon of Ca2 paradox that might be implicated in ischemia reperfusion injury and c how ROS RNS and mitochondrial status could influence the activity of these channels leading to loss of ionic homeostasis and cell death. Background A long-standing perception is that upon activation of glutamate receptors .