title: Polypeptide from Chlamys farreri suppresses ultraviolet-B irradiation-induced apoptosis through restoring ER redox homeostasis, scavenging ROS generation, and suppressing the PERK-eIF2a-CHOP pathway in HaCaT cells.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of polypeptide from Chlamys farreri (PCF) on ultraviolet B (UVB) irradiation-induced apoptosis in human keratinocyte HaCaT cells.
  
  
  METHODS
  HaCaT cells were treated with 20 mJ/cm(2) UVB irradiation for 18 h. The cell viability was measured by MTT assay, and apoptosis was detected with Hoechst 33258 staining and caspase-3 activity detection. Protein expression levels were assessed by Western blot analysis, and the intracellular ROS levels were also measured.
  
  
  RESULTS
  Our results from the MTT assay showed that UVB irradiation significantly declined the viability of HaCaT cells, which could be restored by PCF treatment. PCF decreased the apoptosis rate in HaCaT cells treated with UVB irradiation. Moreover, PCF increased the expression levels of PDI and Ero-1a, and scavenged the intracellular ROS. Furthermore, PCF inhibited the expressions of GRP78, p-PERK, p-eIF2a, and CHOP, and suppressed the ER stress-induced apoptosis, in UVB-irradiated HaCaT cells. In addition, the ROS scavenging effect of 4-PBA was less potent than PCF, indicating that ER stress-related ROS production contribute partially to the total ROS level, and ER was not the only target of PCF treatment.
  
  
  CONCLUSIONS
  Our results indicate that PCF inhibits UVB irradiation-induced apoptosis through restoring ER redox homeostasis and suppressing the PERK-eIF2a-CHOP pathway. These findings provide evidence for the application of PCF in the protection of skin from UV irradiation.
authors.affiliation: Department of Stomatology, Medical College of Qingdao University, Qingdao 266003, Shandong, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao 266071, Shandong, China. Electronic address: xiejingqd@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, Hospital of Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D049897:Pectinidae / Q000737:chemistry*; D010455:Peptides / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014466:Ultraviolet Rays; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010455:Peptides; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase
keywords: Endoplasmic reticulum (ER); HaCaT cells; PERK-eIF2a-CHOP pathway; Ultraviolet-B (UVB) irradiation; Unfolded protein response (UPR)