title: Expression and modulation of apoptosis regulatory molecules in human melanocytes: significance in vitiligo.
abstract: Although the aetiology of the hypopigmentary disorder vitiligo is ill understood, it is clear that pigment producing cells are absent from vitiliginous lesional skin. The present study was designed to investigate the possible role of melanocyte-expressed apoptosis regulatory molecules in melanocyte disappearance. Flow cytometric evaluation of p53, p21, Bcl-2 and Bax revealed no differences in in vitro expression levels between normal control and non-lesional melanocytes. Moreover, no in situ immunohistological differences were observed in melanocytes present in control, non-lesional and perilesional skin. However, an enhanced number of p53+ nuclei, in the absence of detectable p21 expression, was detected in involved areas. The observed p53 expression pattern did not involve melanocytes and could be the result of ultraviolet (UV) A irradiation. Further, we showed that UVB is capable of modulating melanocyte-expressed apoptosis regulatory molecules. Consequently, a lethal dose of UVB was given to two groups of cultured normal control and non-lesional melanocytes. No significant differences were found when comparing the percentages and kinetics of UVB-induced apoptosis in these groups. In conclusion, our results indicate that the relative apoptosis susceptibility of melanocytes in vitiligo is comparable with that of normal control cells. It is therefore unlikely that vitiligo is causally related to dysregulation of apoptosis regulatory molecules.
authors.affiliation: Departments of Pathology and Dermatology, Meibergdreef 9, Academic Medical Center, Amsterdam University, 1105 AZ Amsterdam, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: van den Wijngaard
authors.forename: J
authors.initials: J
authors.lastname: Aten
authors.forename: A
authors.initials: A
authors.lastname: Scheepmaker
authors.forename: I C
authors.initials: IC
authors.lastname: Le Poole
authors.forename: A J
authors.initials: AJ
authors.lastname: Tigges
authors.forename: W
authors.initials: W
authors.lastname: Westerhof
authors.forename: P K
authors.initials: PK
authors.lastname: Das
mesh_terms: D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000502:physiology / Q000528:radiation effects; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D014820:Vitiligo / Q000378:metabolism* / Q000503:physiopathology; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein