目的:观测研究下坡(离心)运动对大鼠骨骼肌肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放在量与时程上的影响。此外,测定离子载体的刺激作用,即测定在含与不含(Ca2+离子载体)A23187时Ca2+-ATP酶活性的比值,用以评定囊泡的完整性。方法:成年雄性S...目的:观测研究下坡(离心)运动对大鼠骨骼肌肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放在量与时程上的影响。此外,测定离子载体的刺激作用,即测定在含与不含(Ca2+离子载体)A23187时Ca2+-ATP酶活性的比值,用以评定囊泡的完整性。方法:成年雄性SD大鼠随机分为对照与离心运动组,离心运动的大鼠分别于运动后即刻,4,24,48,72和144h后取样(n=7).离心运动方式采用90min持续跑台下坡运动(-16°;15m/min)。取大鼠红股肌制备组织匀浆,测定肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放。结果:与对照组[19.25±1.38nmol·min-1·(mg protein)-1]相比,肌浆网Ca2+摄取分别于运动后即刻和4h下降了29% and 36%(P<0.05),24h依然降低(P<0.05).肌浆网Ca2+释放与对照组[31.06±2.36nmol·min-1·(mg protein)-1]相比,也分别于运动后即刻和4h下降了37% and 39%(P<0.05),24h持续降低(P<0.05).用含离子载体测定的肌浆网Ca2+-ATP酶活性运动后4h降低了31%(P<0.05),并于运动后24h仍然降低(P<0.05)。运动后,含与不含A23187时测定的Ca2+-ATP酶活性的比值未见显著性改变,表明该运动没有明显改变肌浆网膜的完整性。结论:一次性低强度,长时间下坡运动导致肌浆网功能长时间降低,运动后恢复期两天尚未完全恢复,亦可构成离心运动诱导的骨骼肌某些功能降低的基础。提示这些变化可能产生于离心收缩时肌节长度不匀一性所造成的张力应激。展开更多
Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine...Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine 674(C674) in the sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase 2(SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674 S knock-in mice(SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha(IRE1 a) and spliced X-box binding protein 1(XBP1 s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1 a/XBP1 s pathway inhibitor 4μ8 C. In addition, suppressing the IRE1 a/XBP1 s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2 a, SERCA2 b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1 a/XBP1 s pathway and SERCA2 might be potential targets for PH therapy.展开更多
文摘目的:观测研究下坡(离心)运动对大鼠骨骼肌肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放在量与时程上的影响。此外,测定离子载体的刺激作用,即测定在含与不含(Ca2+离子载体)A23187时Ca2+-ATP酶活性的比值,用以评定囊泡的完整性。方法:成年雄性SD大鼠随机分为对照与离心运动组,离心运动的大鼠分别于运动后即刻,4,24,48,72和144h后取样(n=7).离心运动方式采用90min持续跑台下坡运动(-16°;15m/min)。取大鼠红股肌制备组织匀浆,测定肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放。结果:与对照组[19.25±1.38nmol·min-1·(mg protein)-1]相比,肌浆网Ca2+摄取分别于运动后即刻和4h下降了29% and 36%(P<0.05),24h依然降低(P<0.05).肌浆网Ca2+释放与对照组[31.06±2.36nmol·min-1·(mg protein)-1]相比,也分别于运动后即刻和4h下降了37% and 39%(P<0.05),24h持续降低(P<0.05).用含离子载体测定的肌浆网Ca2+-ATP酶活性运动后4h降低了31%(P<0.05),并于运动后24h仍然降低(P<0.05)。运动后,含与不含A23187时测定的Ca2+-ATP酶活性的比值未见显著性改变,表明该运动没有明显改变肌浆网膜的完整性。结论:一次性低强度,长时间下坡运动导致肌浆网功能长时间降低,运动后恢复期两天尚未完全恢复,亦可构成离心运动诱导的骨骼肌某些功能降低的基础。提示这些变化可能产生于离心收缩时肌节长度不匀一性所造成的张力应激。
基金supported by National Natural Science Foundation of China (31571172 and 81870343 to Xiaoyong Tong,81700237 to Pingping Hu)Chongqing Natural Science Foundation (cstc2021jcyj-msxmX 0043 to Xiaoyong Tong,China)+1 种基金Chongqing Research Program of Basic Research and Frontier Technology (cstc2016jcyjA 0407 to Xiaoyong Tong,China)Fundamental Research Funds for the Central Universities (2018CDQYYX0042 to Xiaoyong Tong,and 2018CDYXYX0027 to Pingping Hu,China)。
文摘Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine 674(C674) in the sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase 2(SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674 S knock-in mice(SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha(IRE1 a) and spliced X-box binding protein 1(XBP1 s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1 a/XBP1 s pathway inhibitor 4μ8 C. In addition, suppressing the IRE1 a/XBP1 s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2 a, SERCA2 b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1 a/XBP1 s pathway and SERCA2 might be potential targets for PH therapy.
