title: Identification and characterization of ABCB1-mediated and non-apoptotic sebum secretion in differentiated hamster sebocytes.
abstract: 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.
authors: Department of Biochemistry and Molecular Biology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors: Hirokazu
authors: H
authors: Kurihara
authors: Takashi
authors: T
authors: Sato
authors: Noriko
authors: N
authors: Akimoto
authors: Takayuki
authors: T
authors: Ogura
authors: Akira
authors: A
authors: Ito
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000152:Acne Vulgaris / Q000378:metabolism* / Q000473:pathology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D006224:Cricetinae; D003524:Cyclosporins / Q000494:pharmacology; D012628:Dermatitis, Seborrheic / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D010718:Phosphatidylserines / Q000032:analysis; D012235:Rhodamines / Q000032:analysis; D012627:Sebaceous Glands / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012629:Sebum / Q000378:metabolism*; D014280:Triglycerides / Q000032:analysis / Q000096:biosynthesis; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000906:Antibodies; D002121:Calcium Channel Blockers; D003524:Cyclosporins; D007328:Insulin; D010718:Phosphatidylserines; D012235:Rhodamines; D014280:Triglycerides; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D014700:Verapamil; C070272:valspodar