title: Molecular mechanism of polypeptides from Chlamys farreri (PCF)'s anti-apoptotic effect in UVA-exposed HaCaT cells involves HSF1/HSP70, JNK, XO, iNOS and NO/ROS.
abstract: This study investigated the molecular mechanisms of polypeptides from Chlamys farreri (PCF)'s anti-apoptotic effects in ultraviolet A-rays (UVA) exposed HaCaT cells. UVA-induced apoptosis in HaCaT cells was confirmed with Hoechst 33258 fluorescent staining; PCF treatment inhibited UVA-induced apoptosis in HaCaT cells, increased transcriptional activities of heat shock factor protein 1 (HSF1) and the expression of heat shock protein 70 (HSP70), whereas inhibited activation of c-Jun N-terminal kinases (JNK), expression of xanthine oxidese (XO), inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO)/reactive oxygen species (ROS). Meanwhile, the HSF1 transcription inhibitor quercetin increased UVA-induced apoptosis, activation of JNK, expression of XO and iNOS and release of NO/ROS. Among the two NO release peaks we found in UVA exposed HaCaT cells, XO inhibitor oxypurinol was found to be able to inhibit NO release at 3h post UVA exposure but not 18h, while iNOS inhibitor S-methylisothiourea sulfate (SMT) was found to inhibit iNOS expression and NO release at 18h but not 3h. PCF's protection against UVA-induced apoptosis in HaCaT cells involves increased transcriptional activity of HSF1, increased expression of HSP70, and the subsequential inhibition of JNK pathway, XO and iNOS expression and ROS/NO release.
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China; Qingdao Institute for Drug Control, Chemistry Department, 7 Longde Road, Qingdao 266071, Shandong, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
authors.forename: Qixiao
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Qingdao University Medical College, 308 Ningxia Road, Qingdao 266071, Shandong, China. Electronic address: cbwang666@126.com.
authors.forename: Chunbo
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D060125:Characiformes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014969:Xanthine Oxidase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D010455:Peptides; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D048670:MAP Kinase Kinase 4
keywords: Heat shock protein 70; Heat shock transcription factor 1; Inducible nitric oxide synthase; Ultraviolet A-induced apoptosis; Xanthine oxidase; c-Jun N-terminal kinases