title: Transient glucose deprivation causes upregulation of heme oxygenase-1 and cyclooxygenase-2 expression in cardiac fibroblasts.
abstract: Transient glucose deprivation (TGD) has been shown to induce a resistance to a subsequent ischemia and reperfusion injury in the heart. Induction of cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) is known to mediate the powerful defensive adaptation of the heart against oxidative stress. In this study, we found that a 30-min incubation in the absence of glucose resulted in a rapid increased expression of COX-2 and HO-1 in cardiac fibroblasts as examined by real-time quantitative polymerase chain reaction (PCR) and western blot analysis. Interestingly, TGD increased the generation of reactive oxygen species (ROS) and caused the transient phosphorylation of p38 mitogen-activated protein kinase (MAPK) as well as the translocation of protein kinase C (PKC)- from the cytosolic to the membrane fraction. However, no significant change in the distribution of PKC-delta isoform was observed compared with the control. Pretreatment of the cells with an antioxidant, N-acetylcysteine (NAC), resulted in the inhibition of p38 MAPK phosphorylation and PKC- translocation during TGD. In addition, the induction of COX-2 and HO-1 expression by TGD was prevented by pretreatment with NAC or SB203580, a p38 MAPK inhibitor. Surprisingly, pretreatment with chelerythrine, an inhibitor of PKC, strongly augmented the HO-1 mRNA expression but blocked the COX-2 mRNA induction by TGD. These results demonstrate that briefly removing glucose from cultured cardiac fibroblasts induces COX-2 and HO-1 expression via generation of ROS and p38 MAPK phosphorylation, while the translocation of PKC- to the membrane fraction may participate in the induction of COX-2 but not in the HO-1 expression.
authors.affiliation: Division of cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920 0293, Japan. ktakeda@kanazawa-med.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeda
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Shinji
authors.initials: S
authors.lastname: Okubo
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Akazawa-Kudoh
authors.forename: Koji
authors.initials: K
authors.lastname: Kajinami
authors.forename: Seiyu
authors.initials: S
authors.lastname: Kanemitsu
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Tsugawa
authors.forename: Tsugiyasu
authors.initials: T
authors.lastname: Kanda
authors.forename: Shinobu
authors.initials: S
authors.lastname: Matsui
authors.forename: Noboru
authors.initials: N
authors.lastname: Takekoshi
mesh_terms: D000470:Alkaloids; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing); D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D010105:Oxygenases / Q000235:genetics*; D010617:Phenanthridines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000470:Alkaloids; D000975:Antioxidants; D053119:Benzophenanthridines; D006360:Heat-Shock Proteins; D007093:Imidazoles; D007527:Isoenzymes; D010617:Phenanthridines; D011725:Pyridines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C016299:chelerythrine; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580