The expression of peripheral benzodiazepine receptors in human skin: the relationship with epidermal cell differentiation

The peripheral benzodiazepine receptor (PBR) is a protein of mitochondrial outer membranes utilizing porphyrins as endogenous ligands. PER is part of a heteromeric receptor complex involved in the formation of mitochondrial p ermeability transition pores and in the early events of apoptosis. PER may function as an oxygen-dependent signal generator; recent data indicate that these receptors may preserve the mitochondria of haematopoietic cell lines from damage caused by oxygen radicals. To identify PBRs in human skin, we used a specific monoclonal antibody directed against the C-terminus fragmen t of the human receptor. PER immunoreactivity was found in keratinocytes, L angerhans cells, hair follicles and dermal vascular endothelial cells. Inte restingly, confocal microscopic examination of skin sections revealed that PBR expression was strongly upregulated in the superficial differentiated l ayers of the epidermis. Ultrastructurally, PBRs were distributed throughout the cytoplasm but were selectively expressed an the mitochondrial membrane s of epidermal cells. The elevated level of PBRs in the spinous layer was n ot associated with an increased number of mitochondria nor with an increase d amount of mRNA as assessed by in situ hybridization on microautoradiograp hed skin sections. The present work provides, for the first time, evidence of PER immunoreactivity in human skin. This mitochondrial receptor may modu late apoptosis in the epidermis; its increased expression in differentiated epidermal layers may represent a novel mechanism of natural skin protectio n against free radical damage generated by ultraviolet exposure.