Coordinate downregulation of CaM kinase II and phospholamban accompanies contractile phenotype transition in the hyperthyroid rabbit soleus.
Coordinate downregulation of CaM kinase II and phospholamban accompanies contractile phenotype transition in the hyperthyroid rabbit soleus.
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DOI：
10.1152/ajpcell.00352.2003
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发表时间：
2004-04
期刊：
影响因子：
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通讯作者：
M. Jiang;A. Xu;D. Jones;N. Narayanan
中科院分区：
文献类型：
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作者：
M. Jiang;A. Xu;D. Jones;N. Narayanan
本研究探讨了l-甲状腺素诱导的甲状腺功能亢进对兔慢缩比目鱼肌Ca(2+)/钙调素（CaM）依赖蛋白激酶（CaM kinase II）介导的肌浆网（SR）蛋白磷酸化、SR Ca（2+）泵（Ca(2+)- atp酶）活性和收缩持续时间的影响。内源性CaM激酶II对Ca(2+)- atp酶和磷蛋白（PLN）的磷酸化作用在甲亢兔比目鱼肌中显著低于正常甲状腺兔（30-50%）。Western blotting分析显示，甲亢兔比目鱼肌中sarco（endo）质网Ca(2+)- atp酶（SERCA） 1（约150%）Ca（2+）泵异型水平较高，SERCA2 Ca（2+）泵异型水平不变，PLN（约50%）和δ， β -和γ - cam激酶II（40约70%）水平较低。与正常甲状腺对照相比，甲状腺功能亢进的兔比目鱼SR囊泡的Ca（2+）摄取和Ca（2+）刺激的atp酶活性大约高两倍。Ca（2+）吸收V(max)（以nmol Ca（2+）为单位）。mg SR蛋白（-1）。Min(-1)：正常甲状腺，818 +/- 73；甲亢，1,649 +/- 90)，但Ca(2+)- atp酶对Ca（2+）的表观亲和力（正常甲状腺，0.97 +/- 0.02 μ m，甲亢，1.09 +/- 0.04 μ m）在两组之间差异不显著。与甲状腺功能亢进患者相比，CaM激酶ii介导的比目鱼肌SR对Ca（2+）摄取的刺激约低60%。甲状腺机能亢进患者原位测得比目鱼肌等距抽动力明显较大（约36%），达到力峰时间和松弛时间明显较短（约30-40%）。这些结果表明，甲状腺激素诱导的兔比目鱼肌收缩特性的转变与PLN和CaM激酶II的表达和功能的协调下调以及SERCA1的表达和功能的选择性上调有关，而不是SERCA2， SR Ca（2+）泵的异构体。
This study investigated the effects of l-thyroxine-induced hyperthyroidism on Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaM kinase II)-mediated sarcoplasmic reticulum (SR) protein phosphorylation, SR Ca(2+) pump (Ca(2+)-ATPase) activity, and contraction duration in slow-twitch soleus muscle of the rabbit. Phosphorylation of Ca(2+)-ATPase and phospholamban (PLN) by endogenous CaM kinase II was found to be significantly lower (30-50%) in soleus of the hyperthyroid compared with euthyroid rabbit. Western blotting analysis revealed higher levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 1 ( approximately 150%) Ca(2+) pump isoform, unaltered levels of SERCA2 Ca(2+) pump isoform, and lower levels of PLN ( approximately 50%) and delta-, beta-, and gamma-CaM kinase II (40 approximately 70%) in soleus of the hyperthyroid rabbit. SR vesicles from hyperthyroid rabbit soleus displayed approximately twofold higher ATP-energized Ca(2+) uptake and Ca(2+)-stimulated ATPase activities compared with that from euthyroid control. The V(max) of Ca(2+) uptake (in nmol Ca(2+).mg SR protein(-1).min(-1): euthyroid, 818 +/- 73; hyperthyroid, 1,649 +/- 90) but not the apparent affinity of the Ca(2+)-ATPase for Ca(2+) (euthyroid, 0.97 +/- 0.02 microM, hyperthyroid, 1.09 +/- 0.04 microM) differed significantly between the two groups. CaM kinase II-mediated stimulation of Ca(2+) uptake by soleus muscle SR was approximately 60% lower in the hyperthyroid compared with euthyroid. Isometric twitch force of soleus measured in situ was significantly greater ( approximately 36%), and the time to peak force and relaxation time were significantly lower ( approximately 30-40%), in the hyperthyroid. These results demonstrate that thyroid hormone-induced transition in contractile properties of the rabbit soleus is associated with coordinate downregulation of the expression and function of PLN and CaM kinase II and selective upregulation of the expression and function of SERCA1, but not SERCA2, isoform of the SR Ca(2+) pump.