Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-κB signaling

Abstract

Obesity has been implicated in several diseases including cancer, however, the relationship of obesity and susceptibility to ultraviolet (UV) radiation-caused skin diseases has not been investigated. As UV-induced oxidative stress has been implicated in several skin diseases, we assessed the role of obesity on UVB-induced oxidative stress in genetically obese Lep ob /Lep ob (leptin-deficient) mice. Here, we report that chronic exposure to UVB (120 mJ/cm 2 ) resulted in greater oxidative stress in the skin of obese mice in terms of higher levels of H 2 O 2 and NO production, photo-oxidative damage of lipids and proteins, and greater depletion of antioxidant defense enzymes, like, glutathione, glutathione peroxidase and catalase. As UV-induced oxidative stress mediates activation of MAPK and NF-κB signaling pathways, we determined the effect of UVB on these pathways in obese mice. Exposure of obese mice to UVB resulted in phosphorylation of ERK1/2, JNK and p38 proteins of the MAPK family. Compared to wild-type mice, the obese mice exhibited higher levels of phosphorylation of these proteins, greater activation of NF-κB/p65, and higher levels of circulating proinflammatory cytokines, including TNF-α, IL-1-β and IL-6, on UVB irradiation. Together, our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVBinduced oxidative stress, and therefore may be a risk factor for skin diseases associated with UVBinduced oxidative stress.

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

“…Strongly induced mRNA levels of several MMPs in obesity, as well as their role in adipocyte differentiation, might represent a potential molecular link between obesity and cancer (129,130). Oxidative stress, as part of chronic inflammation, may also create a microenvironment favorable to tumor development in obesity (131).…”

Oxidative Stress and Skin Cancer: An Overview

“…The incidence of lipid peroxidation (LPO) in the biological membrane is a free radical-mediated event that is regulated by the availability of substrates in the form of polyunsaturated fatty acids (PUFAs), pro-oxidants which promote peroxidation [24]. LPO is highly detrimental to cell membrane structure and function, and its elevated level has been linked to damaging effects such as loss of fluidity, inactivation of membrane enzymes, increases cell membrane permeability which may ultimately lead to disruption of cell membrane potential [25].…”

A Novel Mechanism of γ-Irradiation-Induced IL-6 Production Mediated by P2Y11 Receptor in Epidermal Keratinocytes

“…53) In this study, the decrease of G9a after γ-irradiation may be involved in the sustained activation of DNA damage markers and repair factors. Although both UV and γ-rays induce the production of IL-6 via p38 MAPK and NF-κB, 54) their different effects in causing SSBs and DSBs, respectively, may be related to the difference in the change of G9a and in the production time of IL-6. In other words, it is thought that γ-irradiation-induced DSB induces reduction of G9a expression, which also causes DNA damage, and the difference in the production time of IL-6.…”