IS THERE A ROLE FOR ROS SIGNALING IN PROLONGED HYPOXIA?
Although ROS signaling is not regarded as central to CCH, it may be that a role for ROS signaling in prolonged hypoxia has not been precluded, and, for example, HIF-1 activation in hypoxia is regulated by redox mechanisms in the dopaminergic PC-12 cell line (1). In examination of potential hypoxia-sensing mechanisms using a cardiac myocyte model, Chandel and Shumacker (3) have proposed a key sensing role for elevated cellular ROS based on initial studies on hypoxic cardiac myocytes (3, 6). This elevated cellular ROS is postulated to occur in hypoxia as a result of a decreased reduction of O2 to H2O by cytochrome oxidase, resulting in a release of electrons upstream at complex III of the mitochondrial electron transport chain and consequently generation of superoxide (6). Although this cardiac myocyte study was based on 1–2 h of hypoxia (a relatively short duration of hypoxia), a number of related investigations illustrate the potential for a key contribution of ROS generation in prolon
