Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

Figure 1

The role of HSPs in oxidative stress and I/R injury—selected signal pathways. Ischemia/reperfusion (I/R) leads to the production of large amounts of reactive oxygen species (ROS), which can lead to further cellular damage. Both ROS and hypoxia (through hypoxia-induced factor) can activate the transcription factor HSF1 (heat shock factor 1). Activation of HSP gene expression involves the stress-inducible conversion of HSF1 from the inactive monomer to the DNA-binding competent homotrimer. HSF1 activates Nrf2 (nuclear factor erythroid-derived 2-like 2) through increased expression of p62 (p62 not shown). The cardioprotective function of Nrf2 in I/R injury results from an activation of the prosurvival PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) kinase pathway but also from activating antioxidant systems. New data revealed a potential crosstalk between Keap1/Nrf2 (Kelch-like ECH-associated protein 1) and Hsp90/HSF1 cytoprotective pathways and the possibility of their comodulation. Other cellular pathways involved in ROS-HSPs-I/R interactions are ERK1/2 (extracellular signal-regulated kinase 1/2) and p38 MAPK (p38 mitogen-activated protein kinases). In addition, HSPs may interact with antioxidant systems or function “hand in hand”. Physical exercises increase both the expression of HSPs and, on the one hand, the formation of ROS and affect the oxidative-antioxidant balance. SOD: superoxide dismutase; CAT: catalase.