title: 5-Aminoimidazole-4-carboxyamide-1-β-D-ribofranoside stimulates the rat enhancer of split- and hairy-related protein-2 gene via atypical protein kinase C lambda.
abstract: The 5'-AMP-activated protein kinase (AMPK) functions as a cellular energy sensor. 5-Aminoimidazole-4-carboxyamide-1-β-D-ribofranoside (AICAR) is a chemical activator of AMPK. In the liver, AICAR suppresses expression of thephosphoenolpyruvate carboxykinase(PEPCK) gene. The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin-inducible transcriptional repressor and its target is thePEPCKgene. In this study, we examined an issue of whether theSHARP-2gene expression is regulated by AICAR via the AMPK. AICAR increased the level of SHARP-2 mRNA in H4IIE cells. Whereas an AMPK inhibitor, compound-C, had no effects on the AICAR-induction, inhibitors for both phosphoinositide 3-kinase (PI 3-K) and protein kinase C (PKC) completely diminished the effects of AICAR. Western blot analyses showed that AICAR rapidly activated atypical PKC lambda (aPKCλ). In addition, when a dominant negative form of aPKCλ was expressed, the induction of SHARP-2 mRNA level by AICAR was inhibited. Calcium ion is not required for the activation of aPKCλ. A calcium ion-chelating reagent had no effects on the AICAR-induction. Furthermore, the AICAR-induction was inhibited by treatment with an RNA polymerase inhibitor or a protein synthesis inhibitor. Thus, we conclude that the AICAR-induction of theSHARP-2gene is mediated at transcription level by a PI 3-K/aPKCλ pathway.
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yanagisawa
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Maya
authors.initials: M
authors.lastname: Moriizumi
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Honami
authors.initials: H
authors.lastname: Yokouchi
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Otsuka
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Mizuki
authors.initials: M
authors.lastname: Aoyagi
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Akiko
authors.initials: A
authors.lastname: Tsukada
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanai
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Ayumi
authors.initials: A
authors.lastname: Haneishi
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan;
authors.forename: Kosuke
authors.initials: K
authors.lastname: Asano
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Ono
authors.affiliation: Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi, Osaka 584-8540, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tomita
authors.affiliation: Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; kazuya.yamada@matsu.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamada
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D000099293:Protein Kinase C-lambda
chemical_list: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D003513:Cycloheximide; D003609:Dactinomycin; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011500:Protein Synthesis Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D012319:RNA Polymerase II; D012333:RNA, Messenger; D012263:Ribonucleosides; D000099293:Protein Kinase C-lambda; C491538:Bhlhe40 protein, rat; C516138:dorsomorphin; C011651:acadesine; C582554:Pck1 protein, rat
keywords: 5′-AMP-activated protein kinase; AICAR; SHARP-2; atypical protein kinase C lambda; insulin-inducible transcriptional repressor