Phospho-Ablated Id2 Is Growth Suppressive and Pro-Apoptotic in Proliferating Myoblasts

Inhibitor of differentiation protein-2 (Id2) is a dominant negative helix-loop-helix (HLH) protein, and a positive regulator of proliferation, in various cells. The N-terminal region of Id2 contains a consensus cdk2 phosphorylation sequence SPVR, which may be involved with the induction of apoptosis, at least in myeloid 32d.3 cells. However, the role of Id2 phosphorylation at serine 5 in skeletal muscle cells is unknown. The objective of this study was to determine if the phosphorylation of Id2 at serine 5 alters its cellular localization and its role in apoptosis in C2C12 myoblasts. Overexpression of wild type Id2 decreased MyoD protein expression, which corresponded to the increased binding of Id2 to basic HLH proteins E47 and E12. Bromodeoxyuridine incorporation was significantly decreased by the overexpression of phospho-ablated Id2 (S5A); conversely, overexpression of wild type Id2 increased cellular proliferation. The subcellular localization of Id2 and phospho-mimicking Id2 (S5D) were predominantly nuclear compared to S5A. The decreased nuclear localization of S5A corresponded to a decrease in cellular proliferation, and an increase in apoptosis. These data suggest that unphosphorylated Id2 is primarily localized in the cytosol, where it is growth suppressive and potentially pro-apoptotic. These results imply that reducing unphosphorylated Id2 may improve the pool of myoblasts available for differentiation by increasing proliferation and inhibiting apoptosis

老化に伴う運動機能低下モデルとしての老化促進マウスの有用性、及びカテキンの運動機能維持作用

京都大学0048新制・論文博士博士(農学)乙第12877号論農博第2804号新制||農||1028(附属図書館)学位論文||H26||N4876(農学部図書室)31595(主査)教授 伏木 亨, 教授 保川 清, 教授 安達 修二学位規則第4条第2項該当Doctor of Agricultural ScienceKyoto UniversityDGA

A to Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 27

Welcome to Part 27, where we finish ‘N’ with nitrates and nootkatone and move onto ‘O’ starting with octacosanol. The first review focuses on what has become quite a hot topic in sport nutrition in the recent years with the BBC leading with a headline in August 2009 that ‘Beetroot Juice boosts Stamina’. The BBC was describing a study from Professor Andy Jones' group: in his brief review for Part 27, he describes the link between supplementing the diet with nitrate-rich beetroot juice to enhance NO availability and the consequential proposed mechanisms that could lead to an improvement in exercise performance. The other two reviews deal with substances that are generally found as plant extracts: nootkatone, a chemical found in the essential oil of grapefruit and other plants including cedars, which is used predominantly as a flavouring compound but also as a natural insecticide; and policosanol, a wheat-germ extract whose main component is octacosanol