NADPH Oxidases and Their Roles in Skin Homeostasis and Carcinogenesis
Jana Rudolf1,2, Houssam Raad1,2, Alain Taieb1,2,3,4
11 Inserm U 1035, Bordeaux, France .
Significance:
Skin protects the body from dehydration, pathogens, and external mutagens. NADPH oxidases are central components for regulating the cellular redox balance. There is increasing evidence indicating that reactive oxygen species (ROS) generated by members of this enzyme family play important roles in the physiology and pathophysiology of the skin. Recent Advances: NADPH oxidases are active producers of ROS such as superoxide and hydrogen peroxide. Different isoforms are found in virtually all tissues. They play pivotal roles in normal cell homeostasis and in the cellular responses to various stressors. In particular, these enzymes are integral parts of redox-sensitive prosurvival and proapoptotic signaling pathways, in which they act both as effectors and as modulators. However, continuous (re)activation of NADPH oxidases can disturb the redox balance of cells, in the worst-case scenario in a permanent manner. Abnormal NADPH oxidase activity has been associated with a wide spectrum of diseases, as well as with aging and carcinogenesis.
Critical Issues:
Sunlight with its beneficial and deleterious effects induces the activation of NADPH oxidases in the skin. Evidence for the important roles of this enzyme family in skin cancer and skin aging, as well as in many chronic skin diseases, is now emerging.
Future Directions:
Understanding the precise roles of NADPH oxidases in normal skin homeostasis, in the cellular responses to solar radiation, and during carcinogenesis will pave the way for their validation as therapeutic targets not only for the prevention and treatment of skin cancers but also for many other skin-related disorders. Antioxid. Redox Signal. 28, 1238-1261.
Insights
NADPH oxidases are key regulators of skin
Area of Science:
- Skin physiology and pathophysiology
- Cellular redox balance
- Reactive oxygen species (ROS) generation
Background:
- NADPH oxidases (NOX) are crucial enzymes producing ROS, impacting skin homeostasis and stress responses.
- NOX enzymes are involved in redox-sensitive signaling pathways, acting as effectors and modulators.
- Dysregulated NOX activity is linked to skin diseases, aging, and cancer.
Purpose of the Study:
- To explore the roles of NADPH oxidases in skin homeostasis.
- To investigate NOX involvement in cellular responses to solar radiation.
- To understand NOX function in skin carcinogenesis.
Main Methods:
- Review of current literature on NADPH oxidases in skin.
- Analysis of NOX isoforms and their functions in skin cells.
- Examination of NOX activity in relation to skin aging and cancer.
Main Results:
- NADPH oxidases are significantly activated by sunlight in the skin.
- Emerging evidence links NOX enzymes to skin cancer, aging, and chronic skin diseases.
- NOX enzymes play dual roles in cell survival and apoptosis.
Conclusions:
- Understanding NOX roles in skin is vital for developing therapeutic strategies.
- Targeting NOX could offer new treatments for skin cancers and other skin disorders.
- Further research on NOX in skin homeostasis and disease is warranted.
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