Oxygen Free Radical Signaling in Ischemic Preconditioning^a

Abstract

This review will focus on the free radical signaling mechanism of preconditioning. The results from our laboratory as well as studies from other laboratories suggest that reactive oxygen species function as second messenger during myocardial adaptation to ischemia. This review provides evidence for the first time that tyrosine kinase and MAP kinases are the targets for reactive oxygen species generated in the preconditioned myocardium. The finding that p38 MAP kinase might be upstream of NF kappa B further supports our previous reports that MAPKAP kinase 2 could be the most likely link between the preconditioning and adaptation mediated by gene expression. p38 activation appears to be an important step in the translocation and activation of the nuclear transcription factor NF kappa B, which in turn may be involved in the induction of the expression of a variety of stress-inducible genes.

Antiapoptotic mechanisms of benidipine in the ischemic/reperfused heart

“…of either those enzymes that directly cause DNA fragmentation, such as calcium-and magnesium-dependent endonuclease (DNase I), or proteins that regulate signal transduction leading to apoptosis, such as calcineurin, calpain and nuclear scaffold protease (Peitsch et al, 1993;McConkey & Orrenius, 1997;Gottlieb & Engler, 1999). Calcium overloading also increases free radical generation (Bagchi et al, 1997), a well-defined apoptosis-inducing factor (Das et al, 1999). Moreover, in cell culture systems, addition of dihydropyridine calcium channel blockers, amlodipine and nifedipine, reduces excessive apoptosis in aging cerebellar granule cells (Mason et al, 1999) and in hypoxic neonatal rat cardiac myocytes (Chen et al, 1998).…”

The kinder side of killer proteases: Caspase activation contributes to neuroprotection and CNS remodeling

“…Indeed, blockade of ROS production decreases the protection afforded by preconditioning. [38][39][40][41][42] Metabolic dysfunction is also a likely contributor to preconditioning. Decline in the ATP/ADP ratio leads to opening of mitochondrial K ATP channels, 43 and activation of these channels increases ROS generation.…”

Killer Proteases and Little Strokes—How the Things that do not Kill You Make You Stronger

“…Reactive oxygen species produced by an oxidizing environment likely increase the opening of K ATP channels via modification of thiol residues within the channels and thus establishing a positive feedback loop for protection (Forbes et al, 2001;Grigoriev et al, 1999;Pain et al, 2000). Preconditioning protection can be blocked with antioxidants and K ATP channel blockers (Baines et al, 1997;Das et al, 1999;Forbes et al, 2001;Lebuffe et al, 2003;Ravati et al, 2001). We hypothesize the major importance of K ATP channel opening during mild ischemia is to enhance the generation of ROS (McLaughlin, 2004(McLaughlin, , 2003.…”