Adaptive Antioxidant Response of Manganese-Superoxide Dismutase Following Repetitive UVA Irradiation

Abstract

In response to the attack of reactive oxygen species, the skin has developed a complex antioxidant defense system including among others the manganese-superoxide dismutase (MnSOD). MnSOD dismutates the superoxide anion (O2*-) derived from the reduction of molecular oxygen to hydrogen peroxide (H2O2), which is detoxified by glutathione peroxidase to water and molecular oxygen. We have addressed the question whether MnSOD is inducible upon UVA irradiation and whether repetitive UV exposure, as practiced for the light-hardening during phototherapy of various photodermatoses, can even enhance the adaptive antioxidant response. Single exposure of four different strains of fibroblasts to UVA irradiation resulted in a dose- and time-dependent increase in specific MnSOD mRNA levels. Interestingly, repetitive UVA exposure at days 1, 2, and 3 at a dose rate of 200 kJ per m2 resulted in a 5-fold induction of specific MnSOD mRNA levels following the third UVA exposure. Similar results were obtained for MnSOD activity. This adaptive response in terms of upregulation of the antioxidant enzyme MnSOD correlates with the protection against high UV doses, if cells were preexposed to sublethal UV doses. Importantly, MnSOD substantially differed between the tested individuals in both mRNA and activity levels. Taken together, we here provide evidence for the increasing induction of MnSOD upon repetitive UVA irradiation that may contribute to the effective adaptive UVA response of the skin during light hardening in phototherapy. Interindividual differences in the inducibility of MnSOD might account for differences in the susceptibility to develop photodermatologic disorders related to photosensitivity, photoaging, and skin cancer. The molecular basis for interindividual differences in the inducibility of antioxidant enzymes remains to be elucidated.

Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

“…The augmentation in apoptotic cells may be due to an increased sensitivity of the opening of the mitochondria transition pore, which is a key event in the intrinsic pathway of apoptosis activated by oxidative stress (48). The up-regulation of Mn-SOD in the epidermis from the elderly is most likely triggered by increased ROS (49,50) derived from a combination of intrinsic changes related to longevity as well as environmental factors, primarily exposure to UV irradiation (photoaging) (Fig. 8).…”

Manganese Superoxide Dismutase Signals Matrix Metalloproteinase Expression via H2O2-dependent ERK1/2 Activation

“…Furthermore, many of the agents that induce the expression of MMP-1 also increase Mn-SOD levels. These agents include TNF (39,40), IL-1 (40,41), UV irradiation (42,43), phorbol esters (44), and in vitro replicative senescence (45).…”

“…Sod2 is the only antioxidant enzyme that is modulated in response to pathogenic stimuli, including lipopolysaccharides, growth factors, and cytokines (40); ionizing radiation (42,43); phorbol esters (44); and redox-cycling drugs and in vitro replicative senescence (45). These findings indicate that cells have evolved to utilize the mitochondria as a major source of the potent intracellular signaling molecule H 2 O 2 via Sod2.…”

Ultraviolet A radiation transiently disrupts gap junctional communication in human keratinocytes

“…UVA has deleterious effects on the human epidermis by generating reactive oxygen species that can degrade lipids, proteins, and DNA and give rise to photo-oxidized products (26). The resulting oxidative stress can damage cellular components and change the pattern of gene expression, leading to photoaging and serious skin diseases such as cancer (20).…”

“…change the pattern of gene expression, leading to photoaging and serious skin diseases such as cancer (20).…”