Enhanced store-operated Ca2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

被引:60
作者
Liu, Xiao-Ru [1 ]
Zhang, Ming-Fang [1 ]
Yang, Na [1 ]
Liu, Qing [1 ]
Wang, Rui-Xing [1 ]
Cao, Yuan-Ning [2 ]
Yang, Xiao-Ru [2 ]
Sham, James S. K. [2 ]
Lin, Mo-Jun [1 ]
机构
[1] Fujian Med Univ, Dept Physiol & Pathophysiol, Fuzhou 350108, Fujian Province, Peoples R China
[2] Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2012年 / 302卷 / 01期
基金
中国国家自然科学基金;
关键词
canonical transient receptor potential 1; store-operated calcium channels; monocrotaline; pulmonary hypertension; endothelin-1; SMOOTH-MUSCLE-CELLS; STROMAL INTERACTION MOLECULE-1; RECEPTOR POTENTIAL EXPRESSION; ACTIVATES CRAC CHANNELS; CALCIUM-ENTRY; INTRACELLULAR CA2+; CATION CHANNEL; ANIMAL-MODELS; UP-REGULATION; I-CRAC;
D O I
10.1152/ajpcell.00247.2011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Liu XR, Zhang MF, Yang N, Liu Q, Wang RX, Cao YN, Yang XR, Sham JS, Lin MJ. Enhanced store-operated Ca2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats. Am J Physiol Cell Physiol 302: C77-C87, 2012. First published September 21, 2011; doi:10.1152/ajpcell.00247.2011.-Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and store-operated Ca2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd3+, La3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCT-induced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.
引用
收藏
页码:C77 / C87
页数:11
相关论文
共 73 条
[1]   Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry Important for Endothelial Cell Proliferation [J].
Abdullaev, Iskandar F. ;
Bisaillon, Jonathan M. ;
Potier, Marie ;
Gonzalez, Jose C. ;
Motiani, Rajender K. ;
Trebak, Mohamed .
CIRCULATION RESEARCH, 2008, 103 (11) :1289-U185
[2]   Medical Treatment of Pulmonary Arterial Hypertension [J].
Adamali, Huzaifa ;
Gaine, Sean P. ;
Rubin, Lewis J. .
SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE, 2009, 30 (04) :484-492
[3]   NIFEDIPINE REDUCES PULMONARY PRESSURE AND VASCULAR TONE DURING SHORT-TERM BUT NOT LONG-TERM TREATMENT OF PULMONARY-HYPERTENSION IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY-DISEASE [J].
AGOSTONI, P ;
DORIA, E ;
GALLI, C ;
TAMBORINI, G ;
GUAZZI, MD .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1989, 139 (01) :120-125
[4]   Na+ entry via store-operated channels modulates Ca2+ signaling in arterial myocytes [J].
Arnon, A ;
Hamlyn, JM ;
Blaustein, MP .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2000, 278 (01) :C163-C173
[5]   TRPC1 store-operated cationic channel subunit [J].
Beech, DJ ;
Xu, SZ ;
McHugh, D ;
Flemming, R .
CELL CALCIUM, 2003, 33 (5-6) :433-440
[6]   Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration [J].
Bisaillon, Jonathan M. ;
Motiani, Rajender K. ;
Gonzalez-Cobos, Jose C. ;
Potier, Marie ;
Halligan, Katharine E. ;
Alzawahra, Wael F. ;
Barroso, Margarida ;
Singer, Harold A. ;
Jourd'heuil, David ;
Trebak, Mohamed .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 298 (05) :C993-C1005
[7]   A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin [J].
Broad, LM ;
Cannon, TR ;
Taylor, CW .
JOURNAL OF PHYSIOLOGY-LONDON, 1999, 517 (01) :121-134
[8]   How valid are animal models to evaluate treatments for pulmonary hypertension? [J].
Campian, Maria E. ;
Hardziyenka, Maxim ;
Michel, Martin C. ;
Tan, Hanno L. .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2006, 373 (06) :391-400
[9]   Pulmonary hypertension in COPD [J].
Chaouat, A. ;
Naeije, R. ;
Weitzenblum, E. .
EUROPEAN RESPIRATORY JOURNAL, 2008, 32 (05) :1371-1385
[10]   Orai1 interacts with STIM1 and mediates capacitative Ca2+ entry in mouse pulmonary arterial smooth muscle cells [J].
ChyuanNg, Lih ;
Ramduny, Deepa ;
Airey, Judith A. ;
Singer, Cherie A. ;
Keller, Phillip S. ;
Shen, Xiao-Ming ;
Tian, Honglin ;
Valencik, Maria ;
Hume, Joseph R. .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 299 (05) :C1079-C1090