H₂O₂preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation

Abstract

Ischemic preconditioning is a complex cardioprotective phenomenon that involves adaptive changes in cells and molecules and occurs in a biphasic pattern: an early phase after 1-2 h and a late phase after 12-24 h. While it is widely accepted that reactive oxygen species are strongly involved in triggering ischemic preconditiong, it is not clear if they play a major role in the early or late phase of preconditioning and which are the mechanisms involved. The present study was designed to investigate the mechanisms behind H(2)O(2)-induced cardioprotection in rat neonatal cardiomyocytes. We focused on antioxidant and phase II enzymes and their modulation by protein kinase signaling pathways and nuclear-factor-E(2)-related factor-1 (Nrf1) and Nrf2. H(2)O(2) preconditioning was able to counteract oxidative stress more effectively in the late than in the early phase of adaptation. In particular, H(2)O(2) preconditioning counteracted oxidative stress-induced apoptosis by decreasing caspase-3 activity, increasing Bcl2 expression and selectively increasing the expression and activity of antioxidant and phase II enzymes through Nrf1 and Nrf2 translocation to the nucleus. The downregulation of Nrf1 and Nrf2 by small interfering RNA reduced the expression level of phase II enzymes. Specific inhibitors of phosphatidylinositol 3-kinase/Akt and p38 MAPK activation partially reduced the cardioprotection elicited by H(2)O(2) preconditioning and the induction and activity of phase II enzymes. These findings demonstrate, for the first time, a key role for Nrf1, and not only for Nrf2, in the induction of phase II enzymes triggered by H(2)O(2) preconditioning.

Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults

“…The PI3K/Akt signaling pathway is also known to be associated with the effect of H 2 O 2 preconditioning [56,57]. However, further studies are needed to understand the effects or mechanisms of Tat-PRAS40 protein in H 2 O 2 preconditioning.…”

Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways

“…Several cytosolic kinases, such as MAPK, PI3K/AKT and PKC, have been shown to modulate Nrf2 and participate in signal transduction from antioxidants and xenobiotics to ARE (35,36). ERK, JNK, and p38 are the primary members of the MAPK family.…”

A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress

“…Cell viability was evaluated by measuring formazan formation as previously reported [64,65]. Briefly, after treatments, cells were incubated with 0.5 mg/mL of MTT solution for 1 h at 37 °C.…”