Progesterone modulates SERCA2a expression and function in rabbit cardiomyocytes

被引：15

作者：

Moshal, Karni S. ^{[1
]}

Zhang, Zhe ^{[1
]}

Roder, Karim ^{[1
]}

Kim, Tae Yun ^{[1
]}

Cooper, Leroy ^{[1
]}

Litvinov, Bogdan Patedakis ^{[1
]}

Lu, Yichun ^{[1
]}

Reddy, Vishal ^{[1
]}

Terentyev, Dmitry ^{[1
]}

Choi, Bum-Rak ^{[1
]}

Koren, Gideon ^{[1
]}

机构：

[1] Brown Univ, Rhode Isl Hosp, Cardiovasc Res Ctr, Warren Alpert Med Sch,Dept Med,Div Cardiol, Providence, RI 02903 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2014年 / 307卷 / 11期

关键词：

long QT syndrome; SERCA2a; hormones; cardiomyocytes; neonate; CARDIAC SARCOPLASMIC-RETICULUM; PROTEIN-LEVELS; GENE-TRANSFER; PHOSPHOLAMBAN; HEART; RESTORATION; CONTRACTION; RELAXATION; SARCOLIPIN; HORMONES;

D O I：

10.1152/ajpcell.00127.2014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo) plasmic reticulum Ca2+-ATPase type 2a (SERCa2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCa2+a expression, thereby reducing Ca2+-dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCa2a regulation in isolated cardiomyocytes. Cardiomyocytes from neonatal (3- to 5-day-old) rabbits were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and sarcoplasmic reticulum-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca2+ transients and Ca2+ clearance was determined using digital imaging. Progesterone treatment increased the total pool of SERCa2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCa2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitin-tagged SERCa2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca2+ transients. Progesterone treatment increases protein levels and activity of SERCa2a. Progesterone stabilizes SERCa2a, in part, by decreasing the ubiquitination level of SERCa2a polypeptides.

引用

页码：C1050 / C1057

页数：8

共 33 条

[1] S-glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide [J].