Preconditioning contractions prevent prolonged force depression and Ca2+-dependent proteolysis of STAC3 after damaging eccentric contractions
Preconditioning contractions prevent prolonged force depression and Ca2+-dependent proteolysis of STAC3 after damaging eccentric contractions
复制标题
预适应收缩可防止破坏性离心收缩后 STAC3 的长期力抑制和 Ca2 依赖性蛋白水解
DOI：
10.1152/japplphysiol.00463.2021
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发表时间：
2021
影响因子：
3.3
通讯作者：
Yamada Takashi
中科院分区：
文献类型：
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作者：
Ashida Yuki;Himori Koichi;Tamai Katsuyuki;Kimura Iori;Yamada Takashi
预处理收缩（PC）已被证明可以显着改善从离心收缩（ECC）诱导的力抑制中恢复。我们在这里研究了PC作用背后的机制，重点是SH 3和富含半胱氨酸的结构域3（STAC 3），这是将膜去极化耦合到肌浆网释放Ca 2+所必需的。在体内暴露于100个重复损伤的ECC后立即（REC 0）、1天（REC 1）和4天（REC 4）切除大鼠内侧腓肠肌（MG）。在损伤性ECC前2天应用具有10次重复非损伤性ECC的PC。在50和100 Hz的刺激频率下，损伤的ECC诱导体内等长扭矩抑制，这伴随着全长STAC 3的量的显著减少，钙蛋白酶1的激活，以及REC 1和REC 4时MG肌肉中伊文思蓝染色阳性纤维的数量增加。有趣的是，PC减弱了所有这些有害的变化引起的损害ECC。此外，对暴露于各种浓度的Ca 2+的正常肌肉样品进行的机制实验显示了STAC 3的Ca 2+依赖性蛋白水解，这被钙蛋白酶抑制剂MDL-28170阻止。总之，PC可以改善损伤ECCs后从力抑制中恢复，部分是通过抑制由于细胞膜通透性增加和随后的钙蛋白酶1激活引起的STAC 3的丢失。新&值得注意的是SH 3和富含半胱氨酸的结构域3（STAC 3）是骨骼肌特异性蛋白，其将膜去极化与肌浆网Ca 2+释放偶联。然而，没有研究检查STAC 3在预处理收缩（PC）对损伤性离心收缩（ECC）的保护作用中的作用。在这里，我们表明，PC可能会改善从损坏的ECC诱导的力抑郁症的恢复，部分通过抑制钙依赖性蛋白水解的STAC 3由于增加膜通透性和随后的钙蛋白酶1激活。
Preconditioning contractions (PCs) have been shown to markedly improve recovery from eccentric contractions (ECCs)-induced force depression. We here examined the mechanism behind the effects of PCs with focusing on the SH3 and cysteine-rich domain 3 (STAC3) that is essential for coupling membrane depolarization to Ca2+release from the sarcoplasmic reticulum. Rat medial gastrocnemius (MG) muscles were excised immediately (REC0), 1 day (REC1), and 4 days (REC4) after exposure to 100 repeated damaging ECCs in vivo. PCs with 10 repeated nondamaging ECCs were applied 2 days before the damaging ECCs. Damaging ECCs induced in vivo isometric torque depression at 50 and 100 Hz stimulation frequencies, which was accompanied by a significant decrease in the amount of full-length STAC3, an activation of calpain 1, and an increased number of Evans Blue dye-positive fibers in MG muscles at REC1 and REC4. Interestingly, PCs attenuated all these deleterious alterations induced by damaging ECCs. Moreover, mechanistic experiments performed on normal muscle samples exposed to various concentration of Ca2+showed a Ca2+-dependent proteolysis of STAC3, which was prevented by calpain inhibitor MDL-28170. In conclusion, PCs may improve recovery from force depression after damaging ECCs, in part by inhibiting the loss of STAC3 due to the increased permeability of cell membrane and subsequent activation of calpain 1.NEW & NOTEWORTHYThe SH3 and cysteine-rich domain 3 (STAC3) is a skeletal muscle-specific protein that couples membrane depolarization to sarcoplasmic reticulum Ca2+release. No studies, however, examined the role of STAC3 in protective effects of preconditioning contractions (PCs) against damaging eccentric contractions (ECCs). Here, we demonstrate that PCs may improve recovery from damaging ECCs-induced force depression, in part by an inhibition of Ca2+-dependent proteolysis of STAC3 due to increased membrane permeability and subsequent calpain 1 activation.