Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion.
Chronic exercise downregulates myocardial myoglobin and attenuates nitrite reductase capacity during ischemia-reperfusion.
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DOI：
10.1016/j.yjmcc.2013.08.002
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发表时间：
2013-11
影响因子：
5
通讯作者：
Calvert, John W.
中科院分区：
文献类型：
--
作者：
Nicholson, Chad K.;Lambert, Jonathan P.;Chow, Chi-Wing;Lefer, David J.;Calvert, John W.
无论是长期训练方案还是短期训练方案，运动对脑梗塞的保护作用都是明显的。在这里，我们比较了亚硝酸盐治疗、自愿运动以及两者结合对心肌缺血-再灌注(MI/R)损伤后的心肌梗死的降低效果。我们还比较了每种策略增加心脏亚硝酸盐水平的程度，以及每种策略对心脏亚硝酸还原酶活性的影响。与久坐不动的小鼠相比，自愿轮跑(VE)4周的小鼠的脑梗塞面积减少了18%，而接受亚硝酸盐治疗(饮用水中为25 mg/L)的小鼠显示出53%的减少。然而，VE和亚硝酸盐的联合使用并不比单独使用VE表现出更好的保护作用。尽管VE组和亚硝酸盐治疗组小鼠的心脏亚硝酸盐水平相似，但VE组小鼠的心脏亚硝酸还原酶活性显著降低。此外，VE后，肌红蛋白(一种已知的亚硝酸盐还原酶)的心脏蛋白表达也减少。进一步研究表明，VE后心脏NFAT活性降低，这是由于钙调神经磷酸酶活性降低和GSK3β活性增加所致。这些数据表明，VE通过抑制钙调神经磷酸酶/NFAT信号而下调心肌肌红蛋白水平。此外，这些结果表明，VE的适度脑梗塞保护作用是由于在MI/R期间心脏将亚硝酸盐还原为一氧化氮的能力降低的结果。
The infarct sparing effects of exercise are evident following both long-term and short-term training regimens. Here we compared the infarct-lowering effects of nitrite therapy, voluntary exercise, and the combination of both following myocardial ischemia-reperfusion (MI/R) injury. We also compared the degree to which each strategy increased cardiac nitrite levels, as well as the effects of each strategy on the nitrite reductase activity of the heart. Mice subjected to voluntary wheel running (VE) for 4 weeks displayed an 18% reduction in infarct size when compared to sedentary mice, whereas mice administered nitrite therapy (25 mg/L in drinking water) showed a 53% decrease. However, the combination of VE and nitrite exhibited no further protection than VE alone. Although the VE and nitrite therapy mice showed similar nitrite levels in the heart, cardiac nitrite reductase activity was significantly reduced in the VE mice. Additionally, the cardiac protein expression of myoglobin, a known nitrite reductase, was also reduced after VE. Further studies revealed that cardiac NFAT activity was lower after VE due to a decrease in calcineurin activity and an increase in GSK3β activity. These data suggest that VE downregulates cardiac myoglobin levels by inhibiting calcineurin/NFAT signaling. Additionally, these results suggest that the modest infarct sparing effects of VE are the result of a decrease in the hearts ability to reduce nitrite to nitric oxide during MI/R.
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影响因子：
20.1
作者：
Calvert JW;Condit ME;Aragón JP;Nicholson CK;Moody BF;Hood RL;Sindler AL;Gundewar S;Seals DR;Barouch LA;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
13.8
作者：
Brunori, M
通讯作者：
Brunori, M
影响因子：
20.1
作者：
Bueno, OF;Lips, DJ;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
64.8
作者：
Garry, DJ;Ordway, GA;Williams, RS
通讯作者：
Williams, RS