Rose Adam J, Kiens Bente, Richter Erik A
Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Universitetsparken 13, Copenhagen, Denmark, 2100.
J Physiol. 2006 Aug 1;574(Pt 3):889-903. doi: 10.1113/jphysiol.2006.111757. Epub 2006 May 11.
Ca2+ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca2+-calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at approximately 67% of peak pulmonary O2 uptake(VO2peak) with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85% VO2peak with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr287 in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr17, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser103, a putative CaMKII substrate, was higher after 30 min of exercise. PLN phosphorylation at Thr17 was higher with increasing exercise intensities. These data indicate that CaMKII is the major multifunctional CaMK in skeletal muscle and its activation occurs rapidly and is sustained during continuous exercise, with the activation being greater during intense exercise.
钙信号传导被认为在运动期间的骨骼肌功能中发挥重要作用。在此，我们检测了多功能钙调蛋白依赖性蛋白激酶（CaMK）在人类骨骼肌中的表达，结果显示CaMKII和CaMKK有表达，而CaMKI或CaMKIV无表达。此外，我们还研究了运动持续时间和强度对骨骼肌CaMKII活性及下游靶点磷酸化的影响。8名健康男性以约67%的峰值肺氧摄取量（VO2peak）进行运动，在静息状态以及运动1、10、30、60和90分钟后采集肌肉样本。另外10名男性以35%、60%和85%VO2peak的强度连续进行三次10分钟的运动，在静息状态、每个运动时段结束时以及运动后30分钟采集肌肉样本。运动期间，骨骼肌中自主CaMKII活性及CaMKII在苏氨酸287位点的磷酸化迅速且短暂增加。此外，在骨骼肌中被确定为CaMKII底物的受磷蛋白（PLN）在苏氨酸17位点的磷酸化在运动后迅速（<1分钟）增加，并且在90分钟的运动过程中一直保持在比基础水平高5倍的磷酸化状态。血清反应因子在丝氨酸103位点的磷酸化，这是一种假定的CaMKII底物，在运动30分钟后更高。随着运动强度增加，PLN在苏氨酸17位点的磷酸化更高。这些数据表明CaMKII是骨骼肌中主要的多功能CaMK，其激活迅速且在持续运动期间持续存在，在剧烈运动时激活程度更高。
