Dual regulation of heat-shock transcription factor (HSF) activation and DNA-binding activity by H2O2: role of thioredoxin.

摘要: The heat-shock (HS) response is a ubiquitous cellular to stress, involving the transcriptional activation of HS genes. Reactive oxygen species (ROS) have been shown regulate activity number transcription factors. We investigated redox regulation stress and report here that in human pre-monocytic line U937 cells, H2O2 induced concentration-dependent transactivation DNA-binding factor-1 (HSF-1). was, however, lower with than HS. thus hypothesized dual HSF by oxidants. found oxidizing agents, such as diamide, well alkylating iodoacetic acid, abolished, vitro, HSF-DNA-binding vivo. effects vitro were reversed sulphydryl reducing agent dithiothreitol endogenous reductor thioredoxin (TRX), while acid irreversible. In addition, TRX also restored oxidized vivo, it was be itself vivo both H2O2. Thus, exerts on HSF: one hand, favours nuclear translocation HSF, other, alters activity, most likely critical cysteine residues within domain. belongs group ROS-modulated propose time required for induction, which may restore provides an explanation delay protein synthesis upon exposure cells ROS.