Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Australia.
J Physiol. 2011 Apr 15;589(Pt 8):2027-39. doi: 10.1113/jphysiol.2011.205468. Epub 2011 Feb 21.
The striated muscle activator of Rho signalling (STARS) is an actin-binding protein specifically expressed in cardiac, skeletal and smooth muscle. STARS has been suggested to provide an important link between the transduction of external stress signals to intracellular signalling pathways controlling genes involved in the maintenance of muscle function. The aims of this study were firstly, to establish if STARS, as well as members of its downstream signalling pathway, are upregulated following acute endurance cycling exercise; and secondly, to determine if STARS is a transcriptional target of peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α) and oestrogen-related receptor-α (ERRα). When measured 3 h post-exercise, STARS mRNA and protein levels as well as MRTF-A and serum response factor (SRF) nuclear protein content, were significantly increased by 140, 40, 40 and 40%, respectively. Known SRF target genes, carnitine palmitoyltransferase-1β (CPT-1β) and jun B proto-oncogene (JUNB), as well as the exercise-responsive genes PGC-1α mRNA and ERRα were increased by 2.3-, 1.8-, 4.5- and 2.7-fold, 3 h post-exercise. Infection of C2C12 myotubes with an adenovirus-expressing human PGC-1α resulted in a 3-fold increase in Stars mRNA, a response that was abolished following the suppression of endogenous ERRα. Over-expression of PGC-1α also increased Cpt-1β, Cox4 and Vegf mRNA by 6.2-, 2.0- and 2.0-fold, respectively. Suppression of endogenous STARS reduced basal Cpt-1β levels by 8.2-fold and inhibited the PGC-1α-induced increase in Cpt-1β mRNA. Our results show for the first time that the STARS signalling pathway is upregulated in response to acute endurance exercise. Additionally, we show in C2C12 myotubes that the STARS gene is a PGC-1α/ERRα transcriptional target. Furthermore, our results suggest a novel role of STARS in the co-ordination of PGC-1α-induced upregulation of the fat oxidative gene, CPT-1β.
横纹肌 Rho 信号转导激活蛋白（STARS）是一种肌动蛋白结合蛋白，特异性表达于心肌、骨骼肌和平滑肌。STARS 被认为提供了一个重要的联系，将外部应激信号转导到细胞内信号通路，从而控制参与肌肉功能维持的基因。本研究的目的首先是确定 STARS 及其下游信号通路成员是否在急性耐力运动后上调；其次是确定 STARS 是否是过氧化物酶体增殖物激活受体γ共激活因子 1-α（PGC-1α）和雌激素相关受体-α（ERRα）的转录靶点。运动后 3 小时，STARS mRNA 和蛋白水平以及肌动蛋白相关转录因子 A（MRTF-A）和血清反应因子（SRF）核蛋白含量分别显著增加 140%、40%、40%和 40%。已知的 SRF 靶基因肉碱棕榈酰转移酶-1β（CPT-1β）和 jun B 原癌基因（JUNB）以及运动反应基因 PGC-1α mRNA 和 ERRα 分别增加 2.3 倍、1.8 倍、4.5 倍和 2.7 倍。用表达人 PGC-1α 的腺病毒感染 C2C12 肌管，导致 Stars mRNA 增加 3 倍，该反应在抑制内源性 ERRα 后被消除。PGC-1α 的过表达还使 Cpt-1β、Cox4 和 Vegf mRNA 分别增加 6.2 倍、2.0 倍和 2.0 倍。内源性 STARS 的抑制使基础 Cpt-1β 水平降低 8.2 倍，并抑制 PGC-1α 诱导的 Cpt-1β mRNA 增加。我们的研究结果首次表明，STARS 信号通路在急性耐力运动后被上调。此外，我们在 C2C12 肌管中表明，STARS 基因是 PGC-1α/ERRα 转录靶点。此外，我们的结果表明 STARS 在协调 PGC-1α 诱导的脂肪氧化基因 CPT-1β 的上调中具有新的作用。
