title: DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage.
abstract: Ketoprofen is widely used to alleviate pain and inflammation in clinical medicine; however, this drug may cause oxidative stress and lead to gastrointestinal (GI) ulcers. We previously reported that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in protecting cells against reactive oxygen species, and it facilitates the prevention of ketoprofen-induced GI mucosal ulcers. Recent reports suggested that Nrf2 becomes unstable in the absence of DJ-1/PARK7, attenuating the activity of Nrf2-regulated downstream antioxidant enzymes. Thus, increasing Nrf2 translocation by DJ-1 may represent a novel means for GI protection. In vitro, caffeic acid increases the nuclear/cytosolic Nrf2 ratio and the mRNA expression of the downstream antioxidant enzymes, ϒ-glutamyl cysteine synthetase, glutathione peroxidase, glutathione reductase, and heme oxygenase-1, by activating the JNK/p38 pathway in Int-407 cells. Moreover, knockdown of DJ-1 also reversed caffeic acid-induced nuclear Nrf2 protein expression in a JNK/p38-dependent manner. Our results also indicated that treatment of Sprague-Dawley rats with caffeic acid prior to the administration of ketoprofen inhibited oxidative damage and reversed the inhibitory effects of ketoprofen on the antioxidant system and DJ-1 protein expression in the GI mucosa. Our observations suggest that DJ-1 plays an important role in caffeic acid-mediated protection against ketoprofen-induced oxidative damage in the GI mucosa.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Cheng
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Ho
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
authors.forename: Jhih-Jia
authors.initials: JJ
authors.lastname: Jhang
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan; Agricultural Biotechnology Center, National Chung Hsing University, 250 Kuokuang Rd., Taichung 40227, Taiwan. Electronic address: gcyen@nchu.edu.tw.
authors.forename: Gow-Chin
authors.initials: GC
authors.lastname: Yen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007660:Ketoprofen / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D064209:Phytochemicals / Q000494:pharmacology; D000071617:Protein Deglycase DJ-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002109:Caffeic Acids; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; D015513:Oncogene Proteins; D064209:Phytochemicals; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007660:Ketoprofen; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005980:Glutathione Reductase; C105131:PARK7 protein, human; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; C040048:caffeic acid
keywords: Caffeic acid; DJ-1; Gastrointestinal ulcer; HO-1; Ketoprofen; NSAIDs; Nrf2