title: Fine-tuned regulation of the PGC-1α gene transcription by different intracellular signaling pathways.
abstract: It has previously been known that transcription of the PGC-1α gene can be either inhibited or stimulated by p38 MAP kinase (p38 MAPK). To determine whether p38 MAPK plays an inhibitory or stimulatory role in PGC-1α gene transcription, we further investigated the role of p38 MAPK in this study. Our results showed that the basal level of p38 MAPK phosphorylation was increased in gastrocnemius of mice under HFD and that p38 MAPK stimulated PGC-1α gene transcription in C(2)C(12) myotubes. Our results also provided new mechanisms in myotubes that the p38 MAPK-induced PGC-1α gene transcription was mediated by CREB. In exploring the role of the Akt-dependent insulin signaling on PGC-1α gene transcription, we found that the basal Akt-dependent signaling was increased in gastrocnemius of mice under HFD. The p38 MAPK-induced PGC-1α gene transcription was prevented by insulin. Insulin suppression of PGC-1α gene transcription was neutralized by overexpression of the constitutively nuclear form of FoxO1. Finally, we located three insulin response elements (IREs) in the PGC-1α promoter, and mutations of these IREs abolish or blunt activity of the PGC-1α promoter. Together, our results show that transcription of the PGC-1α gene is balanced by different intracellular signaling pathways.
authors.affiliation: Translational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.forename: Jie
authors.initials: J
authors.lastname: Ning
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yang
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Jianmin
authors.initials: J
authors.lastname: Han
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
authors.forename: Wenhong
authors.initials: W
authors.lastname: Cao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004041:Dietary Fats / Q000494:pharmacology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D005822:Genetic Vectors; D047468:Immunoprecipitation; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D004041:Dietary Fats; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA; D004247:DNA; D008156:Luciferases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases