PMID- 26590300 OWN - NLM STAT- MEDLINE DCOM- 20161027 LR - 20200601 IS - 1756-2651 (Electronic) IS - 0021-924X (Print) IS - 0021-924X (Linking) VI - 159 IP - 4 DP - 2016 Apr TI - 5-Aminoimidazole-4-carboxyamide-1-beta-D-ribofranoside stimulates the rat enhancer of split- and hairy-related protein-2 gene via atypical protein kinase C lambda. PG - 429-36 LID - 10.1093/jb/mvv116 [doi] AB - The 5'-AMP-activated protein kinase (AMPK) functions as a cellular energy sensor. 5-Aminoimidazole-4-carboxyamide-1-beta-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 (aPKClambda). In addition, when a dominant negative form of aPKClambda was expressed, the induction of SHARP-2 mRNA level by AICAR was inhibited. Calcium ion is not required for the activation of aPKClambda. 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/aPKClambda pathway. CI - (c) The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved. FAU - Komatsu, Yoshiko AU - Komatsu Y AD - Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Yanagisawa, Yuki AU - Yanagisawa Y AD - Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Moriizumi, Maya AU - Moriizumi M AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Tsuchiya, Yuuki AU - Tsuchiya Y AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Yokouchi, Honami AU - Yokouchi H AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Otsuka, Hatsumi AU - Otsuka H AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Aoyagi, Mizuki AU - Aoyagi M AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Tsukada, Akiko AU - Tsukada A AD - Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Kanai, Yukiko AU - Kanai Y AD - Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Haneishi, Ayumi AU - Haneishi A AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Takagi, Katsuhiro AU - Takagi K AD - 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; FAU - Asano, Kosuke AU - Asano K AD - Department of Health and Nutritional Science, Faculty of Human Health Science, Matsumoto University, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan; FAU - Ono, Moe AU - Ono M AD - 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. FAU - Tanaka, Takashi AU - Tanaka T AD - Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi, Osaka 584-8540, Japan. FAU - Tomita, Koji AU - Tomita K AD - Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiorikita, Tondabayashi, Osaka 584-8540, Japan. FAU - Yamada, Kazuya AU - Yamada K AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151120 PL - England TA - J Biochem JT - Journal of biochemistry JID - 0376600 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Bhlhe40 protein, rat) RN - 0 (Homeodomain Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Isoenzymes) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Pyrazoles) RN - 0 (Pyrimidines) RN - 0 (RNA, Messenger) RN - 0 (Ribonucleosides) RN - 10K52CIC1Z (dorsomorphin) RN - 1CC1JFE158 (Dactinomycin) RN - 360-97-4 (Aminoimidazole Carboxamide) RN - 53IEF47846 (acadesine) RN - 98600C0908 (Cycloheximide) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.13 (protein kinase C lambda) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 2.7.7.- (RNA Polymerase II) RN - EC 4.1.1.32 (Pck1 protein, rat) RN - EC 4.1.1.32 (Phosphoenolpyruvate Carboxykinase (GTP)) RN - SY7Q814VUP (Calcium) SB - IM MH - AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/*metabolism MH - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/*genetics MH - Calcium/metabolism MH - Cycloheximide/pharmacology MH - Dactinomycin/pharmacology MH - Enzyme Activation MH - Gene Expression/*drug effects MH - HEK293 Cells MH - Homeodomain Proteins/*genetics MH - Humans MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Isoenzymes/antagonists & inhibitors/genetics/*metabolism MH - Liver/enzymology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphoenolpyruvate Carboxykinase (GTP)/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinase C/antagonists & inhibitors/genetics/*metabolism MH - Protein Synthesis Inhibitors/pharmacology MH - Pyrazoles/pharmacology MH - Pyrimidines/pharmacology MH - RNA Polymerase II/antagonists & inhibitors MH - RNA, Messenger/metabolism MH - Rats MH - Ribonucleosides/*pharmacology MH - Signal Transduction MH - Transcription, Genetic/drug effects PMC - PMC4885932 OTO - NOTNLM OT - 5'-AMP-activated protein kinase OT - AICAR OT - SHARP-2 OT - atypical protein kinase C lambda OT - insulin-inducible transcriptional repressor EDAT- 2015/11/22 06:00 MHDA- 2016/11/01 06:00 PMCR- 2017/04/01 CRDT- 2015/11/22 06:00 PHST- 2015/09/10 00:00 [received] PHST- 2015/10/21 00:00 [accepted] PHST- 2015/11/22 06:00 [entrez] PHST- 2015/11/22 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - mvv116 [pii] AID - 10.1093/jb/mvv116 [doi] PST - ppublish SO - J Biochem. 2016 Apr;159(4):429-36. doi: 10.1093/jb/mvv116. Epub 2015 Nov 20.