LEADER 04934ctm 2200625 i 4500001 ocn136972845 003 OCoLC 005 20230607091859.0 008 070525s2006 xx a bm 000 0 eng d 035 (Sirsi) o136972845 035 (OCoLC)136972845 040 ERE |beng |erda |cERE |dOCLCF |dUMI |dOCLCQ |dOCLCO |dOCL |dOCLCQ |dOCLCO |dOCLCQ |dERE |dUtOrBLW 049 EREE 050 4 QP702.G56 |bJ46 2006 100 1 Jensen, Ellis Benjamin, |eauthor. |?UNAUTHORIZED 245 14 The role of CaMK in the activity dependent regulation of GLUT4 gene expression / |cby Ellis Benjamin Jensen. 264 0 |c2006. 300 128 leaves : |billustrations ; |c28 cm 336 text |btxt |2rdacontent 337 unmediated |bn |2rdamedia 338 volume |bnc |2rdacarrier 502 |bPh. D. |cEast Carolina University |d2006 500 Presented to the faculty of the Department of Exercise and Sport Science. 500 Advisor: G. Lynis Dohm 520 3 The purpose of this study was to test the hypothesis that calcium/calmodulin activated protein kinase (CaMK) and/or calcineurin regulate GLUT4 gene expression in response to altered cellular calcium and to learn ifthis regulation was mediated by myocyte enhancer factor 2 (MEF2) and/or GLUT4 enhancer factor (GEF). To investigate the ability of CaMK and calcineurin to regulate GLUT4, we measured their effect on GLUT4 expression in states where endogenous CaMK and calcineurin activity levels would differ from the basal state. Transgenic mice were chronically exercised and CaMK was shown to activate GLUT4 expression to a similar extent as exercise. There was no further increase in GLUT4 after exercise in CaMK-transgenic mice, suggesting that CaMK activated the same stimulatory pathway as exercise. Nuclear and total MEF2 content was increased both by CaMK and exercise. GEF was not affected by exercise, but was increased in response to CaMKTV expression. There was no effect of exercise or of CaMKIV expression on the MEF2 corepressor, histone deacetylase 5 (HDAC5). CaMKIV overexpression was not able to maintain GLUT4 content in denervated muscle. We proposed that constitutively-active CaMK and/or calcineurin expression would sustain GLUT4 expression if decreased signaling through those enzymes is the cause for the denervation-induced decrease in GLUT4. To determine the mechanism of decreased GLUT4 expression in denervated muscle, assessments were made of MEF2 and GEF binding to the GLUT4 promoter and of their protein content. Denervation decreased GEF binding to the promoter and the content of GEF in the nucleus, but there was no change in either MEF2 binding or MEF2 protein content. To determine the denervation responsive element(s) ofthe GLUT4 promoter, mice expressing a reporter gene driven by different lengths of GLUT4 promoter were denervated. Several different promoter/reporter gene constructs were analyzed, and by measuring reporter gene expression in their denervated muscle, we concluded that the denervation responsive element must be in the basal promoter region. 504 Includes bibliographical references (leaves 110-128). 650 0 Glucose |xPhysiological transport. |=^A12958 650 0 Protein kinases. |=^A396687 650 0 Calcium in the body. |=^A13170 650 0 Genetic transcription |xRegulation. |=^A715339 650 0 Musculoskeletal system. |=^A4330 650 0 Transgenic mice. |=^A328438 650 0 Mice as laboratory animals. |=^A848 650 7 Calcium in the body. |2fast |0(OCoLC)fst00844078 650 7 Genetic transcription |xRegulation. |2fast |0(OCoLC)fst00940102 650 7 Glucose |xPhysiological transport. |2fast |0(OCoLC)fst00943695 650 7 Mice as laboratory animals. |2fast |0(OCoLC)fst01019388 650 7 Musculoskeletal system. |2fast |0(OCoLC)fst01030016 650 7 Protein kinases. |2fast |0(OCoLC)fst01079695 650 7 Transgenic mice. |2fast |0(OCoLC)fst01154669 655 7 Academic theses. |2fast |0(OCoLC)fst01726453 655 7 Academic theses. |2lcgft 655 7 Thèses et écrits académiques. |2rvmgf |0(CaQQLa)RVMGF-000001173 700 1 Dohm, G. Lynis, |edegree supervisor. |?UNAUTHORIZED 710 2 East Carolina University. |bDepartment of Exercise and Sport Science. |?UNAUTHORIZED 856 41 |zAccess via ScholarShip |uhttp://hdl.handle.net/10342/10062 949 Click on web address |wasis |hjoyner101 949 Click on web address |wasis |hhsl111 994 C0 |bERE 596 1 4 998 1082182 998 1082182