肌纤维内肌质网钙漏可能诱发肌钙蛋白抑制亚基降解

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本文以肌钙蛋白抑制亚基(troponin I subunit,TnI)作为肌节蛋白降解的分子标记,探讨舒张期肌纤维内Ca2+浓度升高与肌原纤维降解的关系。采用在收缩期增加肌质网(sarcoplasmic reticulum,SR)钙离子释放通道开放机率的caffeine,以及在舒张期引起SR钙离子释放通道钙漏的H2O2,灌流大鼠离体比目鱼肌,以Western blot技术检测TnI表达水平,并比较其降解程度。结果显示,离体比目鱼肌肌条在40min无钙Krebs液灌流期间,静息张力未见明显改变,发展张力缓慢降低,TnI未发生降解。用低浓度caffeine(1与5mmol/L)灌流肌条,静息张力仅在疲劳收缩期间短暂升高,对肌条疲劳程度与疲劳后的恢复速率均无显著性影响,灌流后肌条的TnI未发生降解;高浓度caffeine(10mmol/L)灌流使静息张力持续升高,肌条易发生疲劳,且疲劳收缩后肌条的发展张力不能恢复,TnI发生明显降解。H2O2灌流对肌条疲劳程度没有明显影响,疲劳收缩后发展张力呈迅速恢复后较快下降,静息张力持续增加,且呈浓度依赖性。用1mmol/L H2O2灌流肌条,TnI未发生降解,用5与10mmol/L H2O2灌流肌条时,TnI降解程度随浓度增大而增加。由于肌条静息张力与舒张期间肌纤维内Ca2+浓度密切相关,以上结果提示,舒张期SR钙离子释放通道钙漏增加,可能引起肌纤维TnI降解。 In this study, troponin I subunit (TnI) was used as a molecular marker for the degradation of sarcomeric proteins to investigate the relationship between elevated Ca2 + concentration and myofibrillar degradation in diastolic myofibers. Caffeine, which increases the openness of Ca2 + release channels in sarcoplasmic reticulum (SR) during systole, and H2O2 which causes Ca2 + leakage in SR Ca2 + release during diastole, was isolated from soleus muscle of rats by Western blot The level of TnI expression was detected and its degree of degradation was compared. The results showed that during the perfusion of calcium-free Krebs fluid in vitro, there was no significant change in resting tension in muscle strips of isolated soleus muscle. The developmental tension decreased slowly and TnI did not degrade. Restraining tension increased only temporarily during fatigue and contraction, and had no significant effect on the degree of fatigue and the rate of recovery after fatigue. The TnI of muscle strips after perfusion No significant degradation was observed. High concentration of caffeine (10 mmol / L) perfusion increased the resting tension, the muscle strips were prone to fatigue, and the tension of the muscle strips after fatigue contraction could not be recovered, TnI was significantly degraded. H 2 O 2 perfusion had no significant effect on the degree of fatigue of myoblasts, and the developmental tension decreased rapidly after fatigue and contracted, resting tension increased continuously and in a concentration-dependent manner. TnI was not degraded by perfusion of muscle strips with 1 mmol / L H 2 O 2. The degradation of TnI increased with increasing concentrations of 5 mmol·L -1 H2O2. As the resting tension of muscle strips is closely related to the intracellular Ca2 + concentration during diastole, the above results suggest that the increase of calcium leakage in diastolic SR calcium release channels may lead to the degradation of muscle fiber TnI.
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