The role of free radicals in endogenous adaptation and intracellular signals

Abstract

Oxidative stress can generate a mass of oxygen free radicals (OFR) in the cells, and these OFRs can induce several acute and chronic symptoms and diseases. If the amount of the generated OFRs overwhelms the antioxidant capacity of the cells, the pathophysiological changes may lead to the death of the cell or the development of chronic degenerative diseases.The phenomenon of ischemic preconditioning has demonstrated the important role of these aggressive and harmful molecules in the endogenous adaptation mechanism of the cells to oxidative stress. After sublethal oxidative stress - mild ischemic insult - the resulting development of a few OFRs can stimulate the intracellular signal-transduction cascade of ischemic preconditioning and, through the induction of severe transcription factors, new antioxidant enzymes and heat shock proteins will be synthesized. These newly synthesized proteins will protect the cellagainst another, more serious oxidative insult in the future.

Keywords: Endogenous adaptation; Free radicals; Ischemic preconditioning; Signal transduction.

Figure 1)

Oxidative balance of the cell: development of oxidative stress. H₂O₂ Hydrogen peroxide; O₂⁻ Superoxide anion; OH• Hydroxyl radical; UV Ultraviolet

Figure 2)

Intracellular signalling of ischemic preconditioning. DAG Diacyl glycerol; IKK Inhibitor kappa kinase; iNOS Inducible nitric oxide synthase; IP3 Inositol triphosphate; Mn-SOD Manganese super-oxide-dismutase; NF-κB Nuclear factor-kappa B; NO nitric oxide; ONOO⁻ Peroxynitrite; PLC and PLD Phospholipase C and D; PIP2 Phosphatidyl inositol diphosphate; PKCɛ Protein kinase Cɛ; ROI Reactive oxygen intermediaries; TyrK Tyrosine kinase