Peroxynitrite: A key molecule in skin tissue response to different types of stress

Abstract

Skin, the largest tissue exposed to a variety of stresses demonstrates a common cellular biochemical response unrelated to the type of the stress allegedly. In this chapter we will describe a phenomenon in which different insults, unrelated to oxidative events to start with, resulted in an activation of common cellular biochemical pathways. These processes are similar to those evoked following exposure to stressors in which oxidants were shown to be the major metabolites involved in the mechanism of damage. This chapter strengthen the hypothesis that peroxynitrite (ONOO-) plays a key role in this common mechanism. Peroxynitrite, a product of the interaction of nitric oxide and superoxide radicals, is a potent and versatile oxidant that can attack a wide range of biological molecules. Therefore, tissue oxidative damage can be diminished by prevention of its production or decreasing its level in the different types of stress. The suggested mechanism of its production in the cell and the different metabolites derived from its decomposition are covered. The literature describing the activation of xanthine oxidase (XO) and nitric oxide synthase (NOS) following exposure of the organism or cells to different types of stress is reviewed. It is suggested that following exposure to the different stressors there is an upregulation of pro-inflammatory cytokines (e.g. TNFα, IL-1β, IL-6 and INFγ). These cytokines may encourage the activation of XO and NOS leading to an enhanced production of peroxynitrite which in turn cause biological damage. These biochemical changes can also be reflected in changes in the cellular redox state of which the total antioxidant capacity (TAC) is one of the major components. Therefore, alteration in TAC following exposure to stress is an important factor in the mechanism of damage. We focus on stressors to skin such as: inflammatory process, exposure to ischemic conditions, diabetic conditions, malignancies, UV irradiation, stretch stress, and effect of drugs. This chapter includes different topics supporting the common mechanism involved in a variety of unrelated stresses. It covers studies of cutaneous injuries in different models (in vivo, ex-vivo, in-vitro) that exhibit the markers mentioned above. © 2008 Springer Netherlands.