The Effects of PPAR-γ Activators on the Growth and Apoptosis of Melanocytes

PURPOSE: Peroxisome proliferator-activated receptors (PPARs) play an important role in cellular responses including proliferation and differentiation. It was reported that 3 subtypes of PPAR are expressed in human melanocytes and activators for PPAR-α and PPAR-γ modulates melanocyte growth and melanogenesis. In this study, I investigated the effects of PPAR-γ activators on melanocyte growth and apoptosis. I further examined the regulation of extracellular signal regulated kinase (ERK) pathway under ciglitazone treatment. METHODS: The growth of melanocytes was measured using the Coulter counter and the effects on pigmentation were investigated with measurement of melanin contents of cultured melanocytes and skin. Apoptosis of cells were detected by TUNEL assay and flow cytometry. The expression of caspase-3 and extracellular signal regulated kinase in melanocytes was measured by Western blot analysis. RESULTS: All three PPAR-γ activators, ciglitazone, troglitazone, and 15d-PGJ₂, inhibited the melanocyte growth in a concentration-dependent fashion. At the highest concentration of 15d-PGJ₂, cytotoxicity was observed by trypan blue assay. Minimal, not statistically significant, increase of melanin content was observed in treatment with troglitazone and 15d-PGJ₂. Statistically significant differences were seen on ciglitazone-treated cells. Ciglitazone also induced pigmentation of cultured skin. Ciglitazone induced apoptosis and increased the expression of caspase 3. Ciglitazone also activated ERK, and mitogen-activated protein kinase kinase 1/2 inhibitor, PD 98059, decreased ciglitazone-induced ERK activation. Pretreatment with PD 98059 significantly prevented against the ciglitazone-induced cell growth inhibition, melanogenesis, and apoptosis. CONCLUSIONS: 1) PPAR-γ activators, ciglitazone, troglitazone, and 15-deoxy-PGJ₂, inhibited cell growth. 2) Ciglitazone increased melanin contents of melanocytes and cultured skin. 3) Ciglitazone inhibited growth of human melanocytes via the induction of apoptosis. 4) The effects of ciglitazone on melanocytes seems to be dependent on ERK signaling pathway.

Author dc:creator

• 이, 중선

Contributors dc:contributor

• 강, 희영
• 대학원 의학과
• 104547

• Melanocyte
• Peroxisome proliferator-activated receptors-γ
• Ciglitazone
• Growth
• Apoptosis
• Extracellular signal regulated kinase
• 멜라닌세포
• 세포고사
• 세포성장
• extracellular signal-regulated protein kinase

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000000326
000000000326

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1279