Alterations in Slow‐Twitch Muscle Phenotype in Transgenic Mice Overexpressing the Ca2+ Buffering Protein Parvalbumin
Alterations in Slow‐Twitch Muscle Phenotype in Transgenic Mice Overexpressing the Ca2+ Buffering Protein Parvalbumin
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过表达 Ca2+ 缓冲蛋白小清蛋白的转基因小鼠慢肌表型的改变
DOI：
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
R. Michel
中科院分区：
文献类型：
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作者：
E. Chin;R. Grange;Francois Viau;Alain R Simard;C. Humphries;J. Shelton;R. Bassel;R. Williams;R. Michel
本研究的目的是确定在慢肌纤维中诱导表达Ca2+缓冲蛋白小白蛋白（PV）是否会导致反映快纤维表型的生理、生化和分子特性的改变。在慢速（I型）肌纤维中产生过表达PV的转基因（TG）小鼠。在比目鱼肌（SOL； 58% I型纤维）中，TG中PV的总表达量比野生型（WT）小鼠高2 - 6倍。最大抽搐张力和强直张力在WT和TG中相似，但在次强直频率（30和50 Hz）下的力在TG SOL中减少。抽搐时间-峰值张力和半松弛时间在TG SOL中显著减少（时间-峰值张力：39.3±2.6 vs. 55.1±4.7 ms；半松弛时间：42.1±3.5 vs. 68.1±9.6 ms， TG和WT分别P < 0.05; n= 8-10）。在TG SOL中，IIa型肌球蛋白重链（MHC）和ryanodine受体在mRNA水平上的表达显著增加，而MHC在蛋白水平上的表达无差异，因此纤维类型无差异。TG - SOL的全肌琥珀酸脱氢酶活性降低了12±0.4%，IIa型纤维的单个纤维甘油- 3 -磷酸脱氢酶活性降低。这些差异与TG SOL中钙调神经磷酸酶活性降低64%有关。这些数据表明，PV的过表达导致钙调神经磷酸酶活性降低，可以改变肌肉的功能和代谢谱，并影响主要是慢抽动肌肉的关键标记基因的表达，而对肌肉收缩蛋白的表达影响很小。
The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow‐twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58 % type I fibres) total PV expression was 2‐ to 6‐fold higher in TG compared to wild‐type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time‐to‐peak tension and half‐relaxation time were significantly decreased in TG SOL (time‐to‐peak tension: 39.3 ± 2.6 vs. 55.1 ± 4.7 ms; half‐relaxation time: 42.1 ± 3.5 vs. 68.1 ± 9.6 ms, P < 0.05 for TG vs. WT, respectively; n= 8–10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 ± 0.4 % in TG SOL and single fibre glycerol‐3‐phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow‐twitch muscle with minimal effects on the expression of muscle contractile proteins.
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影响因子：
3.4
作者：
J. David Johnson;Yandong Jiang;J. Rall
通讯作者：
J. David Johnson;Yandong Jiang;J. Rall
影响因子：
3.2
作者：
FUCHTBAUER, EM;ROWLERSON, AM;JOCKUSCH, H
通讯作者：
JOCKUSCH, H
影响因子：
10.5
作者：
Chin, ER;Olson, EN;Williams, RS
通讯作者：
Williams, RS
DOI：
10.1016/s0021-9258(18)45277-5
发表时间：
1987-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
I. Drummond;A. Lee;E. Resendez;R. Steinhardt
通讯作者：
I. Drummond;A. Lee;E. Resendez;R. Steinhardt
MyoD 和肌细胞生成素 mRNA 在快速和慢速成年骨骼肌中的选择性积累受到神经支配和激素的控制。
DOI：
10.1242/dev.118.4.1137
发表时间：
1993
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Hughes,SM;Taylor,JM;Tapscott,SJ;Gurley,CM;Carter,WJ;Peterson,CA
通讯作者：
Peterson,CA