Free Fatty Acids Induce Lipid Accumulation, Autophagy, and Apoptosis in Human Sebocytes

作者：Amir M. Hossini, Xiaoxiao Hou, Tarik Exner, Beatrix Fauler, Jürgen Eberle, Anja Rabien, Evgenia Makrantonaki, Christos C. Zouboulis · 发表于：Skin Pharmacology and Physiology · 年份：2022 · DOI：10.1159/000527471 · 被引用次数：18 · 研究领域：Acne and Rosacea Treatments and Effects、Retinoids in leukemia and cellular processes、Oral Health Pathology and Treatment

BACKGROUND: A disruption of sebocyte differentiation and lipogenesis has fatal consequences and can cause a wide spectrum of skin diseases, from acne vulgaris to sebaceous carcinoma, however, the relevant molecular mechanisms have not been fully clarified. OBJECTIVES: The induction of autophagy and apoptosis in human sebocytes in response to biologically relevant fatty acids was investigated. METHODS: Free fatty acids (arachidonic acid, linoleic acid, palmitic acid, and palmitoleic acid) and the pan-caspase inhibitor QVD-Oph were added to the supernatant of cultured human SZ95 sebocytes. Individual relevant proteins were analyzed by Western blotting. Apoptosis and cell viability were determined, and typical autophagy structures were detected through electron microscopy. To obtain cell growth curves, cell confluence was continuously monitored by real-time cell analysis. RESULTS: Fatty acids induced the development of intracellular lipid droplets with subsequent apoptosis, whereas arachidonic acid caused the most rapid effect. Cleavage products of caspase-3 were only detected in arachidonic acid-induced apoptosis. The high basal apoptotic rate of cultured SZ95 sebocytes was strongly suppressed by QVD-Oph. Fatty acid-induced apoptosis was also markedly inhibited by QVD-Oph, whereas intracellular lipid droplets further accumulated. While cell viability after incubation with linoleic acid, palmitic acid, or palmitoleic acid and QVD-Oph was comparable with that of non-treated contr...