[Dynamic changes in transcription factor HIF-1alpha, rapid response protein, and membrane structure resistance...

Within the last decade, a great number of reports have discussed cellular redox signalization depending on the levels of oxygen and reactive oxygen species (ROS). Experiments have proven that ROS can not only be damaging, but are also able to induce the synthesis of cell defense systems. The initiation of redox signal system results in the induction of various transcription factors which response to hypoxia and hyperoxia, an increase in ROS, oxidants etc. The most significant of them is HIF-1alpha, transcription factor playing an important role in the regulation of oxygen homeostasis in the cell as well as in resistance of the heart and the brain to ischemic and reperfusion injury. About 60 genes activated by HIF-1 are known today; among these are genes that code defense systems: cellular antioxidant system, peroxiredoxines, prostaglandins, heme oxygenase, and heat shock proteins. However, despite numerous data on HIF-lalpha expression stimulation or suppression in exposure to ischemia or hypoxia, they are rather contradictory. In this study, changes in HIF-la induction three, six, and twelve hours after acute hypoxia (8% O2 during one hour) were evaluated, and the dynamics of HIF-1alpha level following hypoxia was compared with the dynamics of the levels of rapid response protein, such as inducible heme oxygenase form, HSP70 stress inducible protein, and antioxidant defense enzymes. The findings indicate a nonlinear dynamics of changes in the levels of transcription factors and rapid response proteins with protective function, tissue specificity of their induction, a direct correlation between HIF-1alpha and superoxide dismutase levels in the heart and HIF-1alpha and HSP70 levels in the liver. The stability of membrane structures of different organs and cardiac sarcoplasmatic reticulum Ca pump are maintained by activation of redox signalization and compensatory synthesis of defense proteins.