Reactive oxygen species and the modulation of stroke.
Reactive oxygen species and oxidative state are slowly gaining acceptance in having a physiological relevance rather than just being the culprits in pathophysiological processes. The control of the redox environment of the cell provides for additional regulation in relation to critical cellular signal transduction pathways. Conversely, aberrant regulation of oxidative state manifesting as oxidative stress can predispose a cell to adverse outcome. The PI3-kinase/Akt pathway is one such pathway that is partially regulated via oxidative state and, in an oxidative stress paradigm such as ischemic reperfusion injury, may be inactivated, which can lead to potentiation and or exacerbation of cell death. Activation of NF(kappa)B has also been associated with oxidative stress. The role of NF(kappa)B in neuronal cell death is widely debated, with major studies highlighting both a pro- and an antiapoptotic role for NF(kappa)B with the outcome being region, stimulus, dose, and duration specific. This review hopes to make clear that oxidative state plays a key role in the regulation and control of numerous signal transduction pathways in the cell and that elucidating the mechanisms behind oxidative stress-mediated neuronal cell death is important in identifying potential putative targets for the treatment of neuropathologies such as stroke.
Crack
Peter J
PJ
Centre for Functional Genomics & Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, VIC 3168, Australia. peter.crack@med.monash.edu.au
Taylor
Juliet M
JM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology; D016923:Cell Death; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury; D015398:Signal Transduction; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology
D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D010100:Oxygen