title: Apigenin attenuates dopamine-induced apoptosis in melanocytes via oxidative stress-related p38, c-Jun NH2-terminal kinase and Akt signaling.
abstract: BACKGROUND
  Accumulating evidence suggests that the occurrence of oxidative stress leads to melanocyte degeneration in vitiligo. Elevated level of dopamine (DA), an initiator of oxidative stress, reportedly is found in patients with vitiligo and induces melanocyte death in vitro. DA-treated melanocytes have been used as a model to search for antioxidants for treating vitiligo.
  
  
  OBJECTIVE
  We investigated the protective effects of apigenin against DA-induced apoptosis in melanocytes and the molecular mechanism underlying those effects.
  
  
  METHODS
  Melanocytes with or without pretreatment with apigenin were exposed to DA. Then cell viabilities were measured by MTT assay. Cellular reactive oxygen species (ROS) levels and the percentage of apoptotic cells were detected by flow cytometry analysis. Activation of caspase 3, poly(ADP-ribose) polymerase (PARP) and oxidative stress-related signaling, including p38, c-Jun NH2-terminal kinase (JNK) and Akt, were assessed by Western blotting.
  
  
  RESULTS
  Apigenin attenuated DA-induced apoptotic cell death, relieved ROS accumulation and activated caspase 3 and PARP, suggesting the protective effects of apigenin against DA-induced oxidative stress and apoptosis in melanocytes. Moreover, DA induced phosphorylation of p38, JNK and Akt, while inhibitors of p38, JNK and Akt significantly decreased DA-induced apoptosis. However, pretreatment with apigenin significantly inhibited DA-triggered activation of p38, JNK and Akt, suggesting the involvement of p38, JNK and Akt in the protective effects of apigenin against DA-induced cytotoxicity.
  
  
  CONCLUSIONS
  These results suggest that apigenin attenuates dopamine-induced apoptosis in melanocytes via oxidative stress-related p38, JNK and Akt signaling and therefore could be a potential agent in treating vitiligo.
authors.affiliation: Department of Dermatology, the 2nd Affiliated Hospital of Dalian Medical University, No.467 Zhongshan Road, Dalian 116027, Liaoning Province, PR China. lmsleeper@yahoo.com.cn
authors.forename: Mao
authors.initials: M
authors.lastname: Lin
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Lu
authors.forename: Ao-Xue
authors.initials: AX
authors.lastname: Wang
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Qi
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Wang
authors.forename: Mao-Qiang
authors.initials: MQ
authors.lastname: Man
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Tu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014820:Vitiligo / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D047310:Apigenin; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D004298:Dopamine