sdz-psc-833 and Acne-Vulgaris

Sebaceous glands secrete sebum onto the skin surface in a holocrine manner and as such a thin lipid layer is formed as a physiological barrier. In the present study, extracellular level of triacylglycerols (TG), a major sebum component, as well as intracellular TG accumulation was augmented in insulin-differentiated hamster sebocytes (DHS). The DHS exhibited phosphatidylserine exposure in an apoptosis-independent manner. In addition, intracellular ATP level and membrane-transporter activity using a substrate, Rhodamine 123, were highly detectable in the DHS rather than in the undifferentiated hamster sebocytes. A membrane-transporter activating reagent, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP), enhanced transporter activity, extracellular TG level, and phosphatidylserine exposure in the DHS. Both transporter activity and TG secretion were suppressed by R-verapamil, a potent membrane-transporter inhibitor, in the BzATP-treated and untreated DHS. Furthermore, the gene expression and production of ATP-binding cassette subfamily B member 1 (ABCB1) were augmented in the DHS. ABCB1 was also detectable in sebaceous glands in the skin of hamsters. Moreover, the cell-differentiation- and BzATP-augmented transporter activity and TG secretion were dose-dependently inhibited by adding not only an ABCB1 antibody but also a selective inhibitor of ABCB1, PSC833. Thus, these results provide novel evidence that ABCB1 is involved in sebum secretion in the DHS, which is associated with non-apoptotic phosphatidylserine exposure and the increased level of intracellular ATP. These findings should accelerate the understanding of sebum secretion occurring in a holocrine-independent manner in sebaceous glands, and may contribute to the development of therapies for sebaceous gland disorders such as acne, seborrhea, and xerosis.

Topics: Acne Vulgaris; Adenosine Triphosphate; Animals; Antibodies; ATP-Binding Cassette Transporters; Calcium Channel Blockers; Cell Differentiation; Cricetinae; Cyclosporins; Dermatitis, Seborrheic; Epithelial Cells; Gene Expression; Humans; Insulin; Male; Phosphatidylserines; Rhodamines; Sebaceous Glands; Sebum; Triglycerides; Verapamil