Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure
Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure
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DOI：
10.1161/01.cir.0000156461.81529.d7
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发表时间：
2005-03-01
期刊：
影响因子：
37.8
通讯作者：
Haworth, RA
中科院分区：
文献类型：
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作者：
Lokuta, AJ;Maertz, NA;Haworth, RA
背景-肌浆网（SR）Ca 2 +-ATP酶（SERCA 2a亚型）活性降低是心力衰竭收缩力降低的主要决定因素。Ca ~（2+）-ATP酶的失活可通过SERCA ~（2a）硝化作用发生。因此，我们调查的作用SERCA 2a硝化在heartfailure.Methods和结果-我们测量SERCA 2a水平和硝基酪氨酸水平的组织从正常和失败的人的心脏使用Western印迹。我们发现，在年龄匹配的组中，特发性扩张型心肌病（DCM）心脏的硝基酪氨酸水平几乎是对照心脏的两倍。硝基酪氨酸主要存在于分子量为SERCA 2a的单一蛋白质中，免疫沉淀证实硝基酪氨酸抗体识别的蛋白质为SERCA 2a。对照组和DCM心肌细胞半松弛时间与硝基酪氨酸/SERCA 2a含量呈正相关（P < 0.01）。在实验中与分离的SR囊泡从猪心，我们还表明，钙泵失活过氧亚硝酸盐暴露，和失活防止蛋白激酶A pretreatment.Conclusions -我们的结论是，SERCA 2a失活硝化可能有助于钙泵衰竭，因此在DCM心力衰竭。
Background - Reduced sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a isoform) activity is a major determinant of reduced contractility in heart failure. Ca2+-ATPase inactivation can occur through SERCA2a nitration. We therefore investigated the role of SERCA2a nitration in heart failure.Methods and Results - We measured SERCA2a levels and nitrotyrosine levels in tissue from normal and failing human hearts using Western blots. We found that nitrotyrosine levels in idiopathic dilated cardiomyopathic (DCM) hearts were almost double those of control hearts in age-matched groups. Nitrotyrosine was dominantly present in a single protein with the molecular weight of SERCA2a, and immunoprecipitation confirmed that the protein recognized by the nitrotyrosine antibody was SERCA2a. There was a positive correlation between the time to half relaxation and the nitrotyrosine/SERCA2a content (P < 0.01) in myocytes isolated from control and DCM hearts. In experiments with isolated SR vesicles from porcine hearts, we also showed that the Ca pump is inactivated by peroxynitrite exposure, and inactivation was prevented by protein kinase A pretreatment.Conclusions - We conclude that SERCA2a inactivation by nitration may contribute to Ca pump failure and hence heart failure in DCM.