Thyroid hormone is required for the phenotype transitions induced by the pharmacological inhibition of calcineurin in adult soleus muscle of rats.
Thyroid hormone is required for the phenotype transitions induced by the pharmacological inhibition of calcineurin in adult soleus muscle of rats.
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成年比目鱼肌中钙调神经磷酸酶的药理学抑制作用所诱导的表型转变需要甲状腺激素。
DOI：
10.1152/ajpendo.00173.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
X. Bigard
中科院分区：
文献类型：
--
作者：
N. Koulmann;L. Bahi;F. Ribera;H. Sanchez;B. Serrurier;R. Chapot;A. Peinnequin;R. Ventura;X. Bigard
本实验旨在研究环孢菌素A(CsA)引起的甲状腺功能减退和钙调神经磷酸酶抑制对比目鱼肌收缩和代谢表型的影响，为控制线粒体生物发生的信号通路提供新的途径。将28只大鼠随机分为4组，甲状腺正常组、甲状腺功能减退组，分别给予CsA(25 mg/kg，N-CsA和H-CsA)或赋形剂(N-VH和H-VH)灌胃3wk。肌肉表型通过MHC谱以及氧化酶和糖酵解酶的活性来评估。我们测量了线粒体含量的主要调节因子--过氧化物酶体增殖物激活受体-γ共激活物-1α(PGC-1α)的mRNA水平。我们还研究了钙调神经磷酸酶催化A亚单位(CNA)在蛋白和转录水平的表达，以及分别受钙调神经磷酸酶活性和甲状腺激素调控的调节性钙调神经磷酸酶抑制蛋白(MCIP)-1和-2的表达。给予CsA后，MHC由慢变快转变为IIA型亚型，这与氧化能力增强有关。甲状腺功能减退症严重降低了快速MHC亚型的表达和氧化能力。在甲状腺激素缺乏的情况下，CsA对肌肉表型的影响被阻断。氧化谱的变化与PGC-1α的变化密切相关，并与p38MAPK的磷酸化有关。甲状腺功能减退症和环孢素A均可降低钙调神经磷酸酶和MCIPs的mRNA水平，但无相加效应。综上所述，这些结果表明，成年肌肉的表型主要受甲状腺状态的控制。钙调神经磷酸酶抑制对缓慢氧化肌肉表型的影响需要甲状腺激素的生理水平。
The present experiment was designed to examine the effects of hypothyroidism and calcineurin inhibition induced by cyclosporin A (CsA) administration on both contractile and metabolic soleus muscle phenotypes, with a novel approach to the signaling pathway controlling mitochondrial biogenesis. Twenty-eight rats were randomly assigned to four groups, normothyroid, hypothyroid, and orally treated with either CsA (25 mg/kg, N-CsA and H-CsA) or vehicle (N-Vh and H-Vh), for 3 wk. Muscle phenotype was estimated by the MHC profile and activities of oxidative and glycolytic enzymes. We measured mRNA levels of the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), the major regulator of mitochondrial content. We also studied the expression of the catalytic A-subunit of calcineurin (CnA) both at protein and transcript levels and mRNA levels of modulatory calcineurin inhibitor proteins (MCIP)-1 and -2, which are differentially regulated by calcineurin activity and thyroid hormone, respectively. CsA-administration induced a slow-to-fast MHC transition limited to the type IIA isoform, which is associated with increased oxidative capacities. Hypothyroidism strongly decreased both the expression of fast MHC isoforms and oxidative capacities. Effects of CsA administration on muscle phenotype were blocked in conditions of thyroid hormone deficiency. Changes in the oxidative profile were strongly related to PGC-1 alpha changes and associated with phosphorylation of p38 MAPK. Calcineurin and MCIPs mRNA levels were decreased by both hypothyroidism and CsA without additive effects. Taken together, these results suggest that adult muscle phenotype is primarily under the control of thyroid state. Physiological levels of thyroid hormone are required for the effects of calcineurin inhibition on slow oxidative muscle phenotype.
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DOI：
--
发表时间：
2000
期刊：
--
影响因子：
--
作者：
K. M. Baldwin;F. Haddad
通讯作者：
K. M. Baldwin;F. Haddad
DOI：
10.1016/s0021-9258(18)77444-9
发表时间：
1990-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Kirschbaum;H. Kucher;A. Termin;A. Kelly;D. Pette
通讯作者：
B. Kirschbaum;H. Kucher;A. Termin;A. Kelly;D. Pette
影响因子：
10.5
作者：
Chin, ER;Olson, EN;Williams, RS
通讯作者：
Williams, RS
DOI：
10.1152/ajpendo.00633.2005
发表时间：
2006-06-01
影响因子：
5.1
作者：
Garcia-Roves, Pablo M.;Huss, Janice;Holloszy, John O.
通讯作者：
Holloszy, John O.
啮齿动物肌肉中的异肌球蛋白分布：甲状腺状态改变的影响。
DOI：
10.1152/jappl.1990.69.1.321
发表时间：
1990
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
--
作者：
Fitzsimons,DP;Herrick,RE;Baldwin,KM
通讯作者：
Baldwin,KM