Raney Marcella A, Turcotte Lorraine P
Deptartment of Kinesiology and Biological Sciences, College of Letters, Arts, and Sciences, University of Southern California, 3560 Watt Way, Los Angeles, CA 90089-0652, USA.
J Appl Physiol (1985). 2008 May;104(5):1366-73. doi: 10.1152/japplphysiol.01282.2007. Epub 2008 Feb 28.
Calcium-calmodulin/dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK1/2) have each been implicated in the regulation of substrate metabolism during exercise. The purpose of this study was to determine whether CaMKII is involved in the regulation of FA uptake and oxidation and, if it is involved, whether it does so independently of AMPK and ERK1/2. Rat hindquarters were perfused at rest with (n = 16) or without (n = 10) 3 mM caffeine, or during electrical stimulation (n = 14). For each condition, rats were subdivided and treated with 10 muM of either KN92 or KN93, inactive and active CaMKII inhibitors, respectively. Both caffeine treatment and electrical stimulation significantly increased FA uptake and oxidation. KN93 abolished caffeine-induced FA uptake, decreased contraction-induced FA uptake by 33%, and abolished both caffeine- and contraction-induced FA oxidation (P < 0.05). Caffeine had no effect on ERK1/2 phosphorylation (P > 0.05) and increased alpha(2)-AMPK activity by 68% (P < 0.05). Electrical stimulation increased ERK1/2 phosphorylation and alpha(2)-AMPK activity by 51% and 3.4-fold, respectively (P < 0.05). KN93 had no effect on caffeine-induced alpha(2)-AMPK activity, ERK1/2 phosphorylation, or contraction-induced ERK1/2 phosphorylation (P > 0.05). Alternatively, it decreased contraction-induced alpha(2)-AMPK activity by 51% (P < 0.05), suggesting that CaMKII lies upstream of AMPK. These results demonstrate that regulation of contraction-induced FA uptake and oxidation occurs in part via Ca(2+)-independent activation of ERK1/2 as well as Ca(2+)-dependent activation of CaMKII and AMPK.
钙调蛋白依赖性蛋白激酶II（CaMKII）、AMP激活的蛋白激酶（AMPK）以及细胞外信号调节激酶（ERK1/2）均与运动过程中底物代谢的调节有关。本研究的目的是确定CaMKII是否参与脂肪酸摄取和氧化的调节，如果参与，其作用是否独立于AMPK和ERK1/2。在静息状态下，用3 mM咖啡因灌注大鼠后肢（n = 16）或不灌注（n = 10），或在电刺激期间（n = 14）进行灌注。对于每种情况，将大鼠分组并用10 μM的KN92或KN93（分别为无活性和有活性的CaMKII抑制剂）进行处理。咖啡因处理和电刺激均显著增加脂肪酸摄取和氧化。KN93消除了咖啡因诱导的脂肪酸摄取，使收缩诱导的脂肪酸摄取降低了33%，并消除了咖啡因和收缩诱导的脂肪酸氧化（P < 0.05）。咖啡因对ERK1/2磷酸化无影响（P > 0.05），并使α(2)-AMPK活性增加了68%（P < 0.05）。电刺激使ERK至1/2磷酸化和α(2)-AMPK活性分别增加了51%和3.4倍（P < 0.05）。KN93对咖啡因诱导的α(2)-AMPK活性、ERK1/2磷酸化或收缩诱导的ERK1/2磷酸化无影响（P > 0.05）。或者，它使收缩诱导的α(2)-AMPK活性降低了51%（P < 0.05），表明CaMKII位于AMPK的上游。这些结果表明，收缩诱导的脂肪酸摄取和氧化的调节部分通过ERK1/2的钙非依赖性激活以及CaMKII和AMPK的钙依赖性激活来实现。
