Zhongcui Sun

Publications (3)26.71 Total impact

• Article: Rad GTPase induces cardiomyocyte apoptosis through the activation of p38 mitogen-activated protein kinase.

  Zhongcui Sun, Ji Zhang, Jifeng Zhang, Chunlei Chen, Quan Du, Lin Chang, Chunmei Cao, Ming Zheng, Minerva T Garcia-Barrio, Yuqing E Chen, Rui-Ping Xiao, Jieming Mao, Xiaojun Zhu
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  ABSTRACT: Rad is a member of a subclass of small GTP-binding proteins, the RGK family. In the present study we investigated the role of Rad protein in regulating cardiomyocyte viability. DNA fragmentation and TUNEL assays demonstrated that Rad promoted rat neonatal cardiomyocyte apoptosis. Rad silencing fully blocked serum deprivation induced apoptosis, indicating Rad is necessary for trigger cardiomyocyte apoptosis. Rad overexpression caused a dramatic decrease of the anti-apoptotic molecule Bcl-x(L), whereas Bcl-x(L) overexpression protected cardiomyocytes against Rad-induced apoptosis. Rad-triggered apoptosis was mediated by the activation of p38 MAPK. The p38 blocker SB203580 effectively protected cardiomyocytes against Rad-evoked apoptosis.
  Biochemical and Biophysical Research Communications 05/2011; 409(1):52-7. · 2.48 Impact Factor
• Article: Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart.

  Gang Wang, Xiaojun Zhu, Wenjun Xie, Peidong Han, Kaitao Li, Zhongcui Sun, Yanru Wang, Chunlei Chen, Ruisheng Song, Chunmei Cao, Jifeng Zhang, Caihong Wu, Jie Liu, Heping Cheng
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  ABSTRACT: Rad (Ras associated with diabetes) GTPase, a monomeric small G protein, binds to Ca(v)beta subunit of the L-type Ca(2+) channel (LCC) and thereby regulates LCC trafficking and activity. Emerging evidence suggests that Rad is an important player in cardiac arrhythmogenesis and hypertrophic remodeling. However, whether and how Rad involves in the regulation of excitation-contraction (EC) coupling is unknown. This study aimed to investigate possible role of Rad in cardiac EC coupling and beta-adrenergic receptor (betaAR) inotropic mechanism. Adenoviral overexpression of Rad by 3-fold in rat cardiomyocytes suppressed LCC current (I(Ca)), [Ca(2+)](i) transients, and contractility by 60%, 42%, and 38%, respectively, whereas the "gain" function of EC coupling was significantly increased, due perhaps to reduced "redundancy" of LCC in triggering sarcoplasmic reticulum release. Conversely, approximately 70% Rad knockdown by RNA interference increased I(Ca) (50%), [Ca(2+)](i) transients (52%) and contractility (58%) without altering EC coupling efficiency; and the dominant negative mutant RadS105N exerted a similar effect on I(Ca). Rad upregulation caused depolarizing shift of LCC activation and hastened time-dependent LCC inactivation; Rad downregulation, however, failed to alter these attributes. The Na(+)/Ca(2+) exchange activity, sarcoplasmic reticulum Ca(2+) content, properties of Ca(2+) sparks and propensity for Ca(2+) waves all remained unperturbed regardless of Rad manipulation. Rad overexpression, but not knockdown, negated betaAR effects on I(Ca) and Ca(2+) transients. These results establish Rad as a novel endogenous regulator of cardiac EC coupling and betaAR signaling and support a parsimonious model in which Rad buffers Ca(v)beta to modulate LCC activity, EC coupling, and betaAR responsiveness.
  Circulation Research 11/2009; 106(2):317-27. · 9.49 Impact Factor
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  Available from: ahajournals.org

  Article: Rad GTPase deficiency leads to cardiac hypertrophy.

  Lin Chang, Jifeng Zhang, Yu-Hua Tseng, Chang-Qing Xie, Jacob Ilany, Jens C Brüning, Zhongcui Sun, Xiaojun Zhu, Taixing Cui, Keith A Youker, Qinglin Yang, Sharlene M Day, C Ronald Kahn, Y Eugene Chen
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  ABSTRACT: Rad (Ras associated with diabetes) GTPase is the prototypic member of a subfamily of Ras-related small G proteins. The aim of the present study was to define whether Rad plays an important role in mediating cardiac hypertrophy. We document for the first time that levels of Rad mRNA and protein were decreased significantly in human failing hearts (n=10) compared with normal hearts (n=3; P<0.01). Similarly, Rad expression was decreased significantly in cardiac hypertrophy induced by pressure overload and in cultured cardiomyocytes with hypertrophy induced by 10 micromol/L phenylephrine. Gain and loss of Rad function in cardiomyocytes significantly inhibited and increased phenylephrine-induced hypertrophy, respectively. In addition, activation of calcium-calmodulin-dependent kinase II (CaMKII), a strong inducer of cardiac hypertrophy, was significantly inhibited by Rad overexpression. Conversely, downregulation of CaMKIIdelta by RNA interference technology attenuated the phenylephrine-induced hypertrophic response in cardiomyocytes in which Rad was also knocked down. To further elucidate the potential role of Rad in vivo, we generated Rad-deficient mice and demonstrated that they were more susceptible to cardiac hypertrophy associated with increased CaMKII phosphorylation than wild-type littermate controls. The present data document for the first time that Rad is a novel mediator that inhibits cardiac hypertrophy through the CaMKII pathway. The present study will have significant implications for understanding the mechanisms of cardiac hypertrophy and setting the basis for the development of new strategies for treatment of cardiac hypertrophy.
  Circulation 12/2007; 116(25):2976-83. · 14.74 Impact Factor