K J Smith1, E Dipreta, H Skelton. 1. Department of Dermatology, National Naval Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889-5600, USA. hskelii@aol.com
Abstract
BACKGROUND: Peroxisomes are small cellular organelles that were almost ignored for years because they were believed to play only a minor role in cellular functions. However, it is now known that peroxisomes play an important role in regulating cellular proliferation and differentiation as well as in the modulation of inflammatory mediators. In addition, peroxisomes have broad effects on the metabolism of lipids, hormones, and xenobiotics. Through their effects on lipid metabolism, peroxisomes also affect cellular membranes and adipocyte formation, as well as insulin sensitivity, and peroxisomes play a role in aging and tumorigenesis through their effects on oxidative stress. OBJECTIVE: To review genetically determined peroxisomal disorders, especially those that particularly affect the skin, and some recent information on the specific genetic defects that lead to some of these disorders. In addition, we present some of the emerging knowledge of peroxisomal proliferator activator receptors (PPARs) and how ligands for these receptors modulate different peroxisomal functions. We also present information on how the discovery of PPARs, and the broad and diverse group of ligands that activate these members of the superfamily of nuclear binding transcription factors, has led to development of new drugs that modulate the function of peroxisomes. CONCLUSION: PPAR expression and ligand modulation within the skin have shown potential uses for these ligands in a number of inflammatory cutaneous disorders, including acne vulgaris, cutaneous disorders with barrier dysfunction, cutaneous effects of aging, and poor wound healing associated with altered signal transduction, as well as for side effects induced by the metabolic dysregulation of other drugs.
BACKGROUND: Peroxisomes are small cellular organelles that were almost ignored for years because they were believed to play only a minor role in cellular functions. However, it is now known that peroxisomes play an important role in regulating cellular proliferation and differentiation as well as in the modulation of inflammatory mediators. In addition, peroxisomes have broad effects on the metabolism of lipids, hormones, and xenobiotics. Through their effects on lipid metabolism, peroxisomes also affect cellular membranes and adipocyte formation, as well as insulin sensitivity, and peroxisomes play a role in aging and tumorigenesis through their effects on oxidative stress. OBJECTIVE: To review genetically determined peroxisomal disorders, especially those that particularly affect the skin, and some recent information on the specific genetic defects that lead to some of these disorders. In addition, we present some of the emerging knowledge of peroxisomal proliferator activator receptors (PPARs) and how ligands for these receptors modulate different peroxisomal functions. We also present information on how the discovery of PPARs, and the broad and diverse group of ligands that activate these members of the superfamily of nuclear binding transcription factors, has led to development of new drugs that modulate the function of peroxisomes. CONCLUSION:PPAR expression and ligand modulation within the skin have shown potential uses for these ligands in a number of inflammatory cutaneous disorders, including acne vulgaris, cutaneous disorders with barrier dysfunction, cutaneous effects of aging, and poor wound healing associated with altered signal transduction, as well as for side effects induced by the metabolic dysregulation of other drugs.