ABSTRACT
Ever since the presence of molecular oxygen in the earth's early atmosphere, living cells have had to adapt to the potential hazards of oxygen, mediated by its metabolites such as superoxide, which may be formed when oxygen is reduced to water. Thus, oxygen toxicity necessitated aerobic as well as anaerobic life forms to develop systems whose function was to rapidly inactivate reactive oxygen species. This might be the reason that the rate of evolution of superoxide dismutase, which catalyzes the reduction of superoxide to hydrogen peroxide (H2O2) is among the fastest observed for any protein (1). There may, however, also be another evolutionary reason for effective H2O2 formation. That is the notion that H2O2 seems to function in signal transduction. For example, the observation that H2O2 can induce viral replication (2) supports a role for H2O2 in basic biochemical processes that control protein synthesis. An important mechanism by which H2O2 acts as a messenger molecule in mammalian cells is through the activation of the transcription factor nuclear factor kappa B (NFKB) (2). Via this pathway H2O2 can induce early gene expression of cytokines (3). In addition, H2O2 may play a prominent role in programmed cell death (4). Since bacterial endotoxin (lipopolysaccharide; LPS) as well as cytokines, such as tumor necrosis factor-a (TNF-a), may stimulate leukocytes and endothelial cells to produce reactive oxygen species, including H2O2, it is obvious that there is an increasing interest in understanding the role of H2O2 in the pathogenesis of inflammatory diseases. In this overview, the role of H2O2 in NFKB-mediated TNF-a synthesis and replication of human immunodeficiency virus (HIV) will be discussed.
