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Tham khảo tài liệu 'acute ischemic stroke part 4', khoa học tự nhiên, công nghệ sinh học phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke 43 antioxidant 133 or by the over-expression of mitochondrial Hsp70 Hsp75 134 both of which decrease the ROS concentration. Although mitochondrial dysfunction has been considered as a major source of ROS other excitotoxic pathways may also be important in inducing oxidative stress. Recently it has been suggested that NADPH oxidase is the primary source of superoxide production following neuronal NMDAR activation 135 . All NADPH oxidase NOX family members are transmembrane proteins that transport electrons across biological membranes. In general the electron acceptor is oxygen and the product of the electron transfer reaction is O2 . The biological function of NOX enzymes is therefore the generation of ROS. NADPH oxidase was originally described in neutrophils but has subsequently been identified in many other cell types including neurons 136 . While NMDAR activation induces O2 production by NADPH oxidase a near-complete absence of O2 production was observed in neurons lacking functional NADPH oxidase and in neurons in which NADPH oxidase function had been inhibited. Markedly reduced NMDA neurotoxicity was also observed under these conditions 137 . During the ischemic phase some Ca2 -dependent enzymes such as phospholipase A2 PLA2 and cyclooxygenase COX produce oxygen free radicals. It has been shown that PLA2 levels increase in the brain within 2-30 min of ischemia 138 . The activation of PLA2 by Ca2 results in the release of arachidonic acid from the phospholipids which is further metabolized by cyclooxygenase to eicosanoids along with the production of free radicals 139 . Cyclooxygenase catalyzes the addition of two O2 molecules to arachidonic acid to produce the prostaglandina PGG2 which in turn is rapidly peroxidized to PGH2 with a simultaneous release of O2 11 140 . In addition PLA2 activation generates lysophosphatides that alter membrane structures. Activation of PLA2 and cyclooxygenase generates .
