The Role of Photolabile Dermal Nitric Oxide Derivates in Ultraviolet Radiation (UVR)-Induced Cell Death

Christian Opländer,Christoph Suschek

doi:10.3390/ijms14010191

Abstract

Human skin is exposed to solar ultraviolet radiation comprising UVB (280–315 nm) and UVA (315–400 nm) on a daily basis. Within the last two decades, the molecular and cellular response to UVA/UVB and the possible effects on human health have been investigated extensively. It is generally accepted that the mutagenic and carcinogenic properties of UVB is due to the direct interaction with DNA. On the other hand, by interaction with non-DNA chromophores as endogenous photosensitizers, UVA induces formation of reactive oxygen species (ROS), which play a pivotal role as mediators of UVA-induced injuries in human skin. This review gives a short overview about relevant findings concerning the molecular mechanisms underlying UVA/UVB-induced cell death. Furthermore, we will highlight the potential role of cutaneous antioxidants and photolabile nitric oxide derivates (NODs) in skin physiology. UVA-induced decomposition of the NODs, like nitrite, leads not only to non-enzymatic formation of nitric oxide (NO), but also to toxic reactive nitrogen species (RNS), like peroxynitrite. Whereas under antioxidative conditions the generation of protective amounts of NO is favored, under oxidative conditions, less injurious reactive nitrogen species are generated, which may enhance UVA-induced cell death.

Highlights

Human skin is exposed to sunlight on a daily basis, and especially, the biological effects of the ultraviolet region namely UVB (280–315 nm) and UVA (315–400 nm) have been investigated intensely in the last decades
It has been hypothesized that photolabile nitric oxide (NO)-related species or compounds, such as nitrite and nitrosothiols, which are stored in comparably high concentration in the skin, can be mobilized by UVA and delivered to the systemic circulation, exerting coronary vasodilation and antihypertensive effects [7,8]
The keratinocytes express the neuronal isoform of NO synthase, whereas the fibroblasts and other cell types in the skin express the endothelial isoform

Summary

Introduction

Human skin is exposed to sunlight on a daily basis, and especially, the biological effects of the ultraviolet region namely UVB (280–315 nm) and UVA (315–400 nm) have been investigated intensely in the last decades. A growing body of studies and data suggest general health benefits of sunlight and UVR-exposure [3]. In this context, in particular, the production of Vitamin D in the deeper epidermis of the skin by UVB and the resulting higher circulating concentrations of serum 25-hydroxyvitamin D may reduce the risk of many chronic and infectious diseases, inter alia, cancer, hypertension and cardiovascular diseases, autoimmune diseases and bacterial and viral infections [4,5,6]. It has been suggested that many of the beneficial effects of sunlight, those related to cardiovascular health, are mediated by mechanisms that are independent of vitamin D production. We will review briefly in this article the common mechanism of UVA- and UVB-induced cell damage and highlight the possible role of NO-related species as endogenous photo-sensitizers, which, especially during UVA exposure, may represent a protective principle against UVA-induced and ROS-mediated cell and tissue damage

UVR-Induced Cell Damage

Physiology of Nitric Oxide

Nitrogen Oxide Derivates as Source of Nitric Oxide

UVA Induces Non-Enzymatic NO-Formation in Human Skin

The Protective Role of Intracellular Nitrite during UVA-Challenge