Tappia Paramjit S, Dent Melissa R, Aroutiounova Nina, Babick Andrea P, Weiler Hope
Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre and Department of Human Nutritional Sciences, Faculties of Human Ecology and Medicine, University of Manitoba, 351 Tache Avenue, Winnipeg, MB R2H 2A6, Canada.
Can J Physiol Pharmacol. 2007 Mar-Apr;85(3-4):465-75. doi: 10.1139/y06-104.
In an earlier study, we showed that dietary conjugated linoleic acid (CLA) isomers can exert differential effects on heart function in male and female rats, but the underlying mechanisms for these actions are not known. Cardiomyocyte Ca2+ cycling is a key event in normal cardiac contractile function and defects in Ca2+ cycling are associated with cardiac dysfunction and heart disease. We therefore hypothesized that abnormalities in the sarcolemmal (SL) and sarcoplasmic reticulum (SR)-mediated regulation of intracellular Ca2+ contribute to altered cardiac contractile function of male and female rats owing to dietary CLA isomers. Healthy male and female Sprague-Dawley rats were fed different CLA isomers, (cis-9, trans-11 (c9,t11) and trans-10, cis-12 (t10,c12)) individually and in combination (50:50 mix as triglyceride or fatty acids) from 4 to 20 weeks of age. We determined the mRNA levels of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 2a, ryanodine receptor, phospholamban, calsequestrin, Na+-Ca2+-exchanger (NCX), and L-type Ca2+ channel in the left ventricle (LV) by RT-PCR. The SR function was assessed by measurement of Ca2+-uptake and -release. Significant gender differences were seen in the LV NCX, L-type Ca2+ channel, and ryanodine receptor mRNA expression levels in control male and female rats. Dietary CLA isomers in the various forms induced changes in the mRNA levels of SERCA 2a, NCX, and L-type Ca2+ channel in the LV of both male and female hearts. Whereas protein contents of the Ca2+ cycling proteins were altered, changes in SR Ca2+-uptake and -release were also detected in both male and female rats in response to dietary CLA. The results of this study demonstrate that long-term dietary supplementation can modulate cardiac gene expression and SR function in a gender-related manner and may, in part, contribute to altered cardiac contractility.
在一项早期研究中，我们发现膳食共轭亚油酸（CLA）异构体对雄性和雌性大鼠的心脏功能可产生不同影响，但其作用的潜在机制尚不清楚。心肌细胞Ca2+循环是正常心脏收缩功能中的关键事件，而Ca2+循环缺陷与心脏功能障碍和心脏病相关。因此，我们推测，由于膳食CLA异构体，肌膜（SL）和肌浆网（SR）介导的细胞内Ca2+调节异常导致雄性和雌性大鼠心脏收缩功能改变。健康的雄性和雌性Sprague-Dawley大鼠从4周龄到20周龄分别单独或联合（以甘油三酯或脂肪酸形式按50:50混合）喂食不同的CLA异构体（顺式-9，反式-11（c9,t11）和反式-10，顺式-12（t10,c12））。我们通过逆转录聚合酶链反应（RT-PCR）测定左心室（LV）中肌浆网/内质网Ca2+-ATP酶（SERCA）2a、兰尼碱受体、受磷蛋白、肌集钙蛋白、钠钙交换体（NCX）和L型Ca2+通道的mRNA水平。通过测量Ca2+摄取和释放来评估SR功能。在对照雄性和雌性大鼠的LV中，NCX、L型Ca2+通道和兰尼碱受体mRNA表达水平存在显著性别差异。各种形式的膳食CLA异构体均可诱导雄性和雌性心脏LV中SERCA 2a、NCX和L型Ca2+通道的mRNA水平发生变化。虽然Ca2+循环蛋白的蛋白质含量发生了改变，但在雄性和雌性大鼠中，响应膳食CLA，也检测到了SR Ca2+摄取和释放的变化。本研究结果表明，长期膳食补充可按性别相关方式调节心脏基因表达和SR功能，并且可能部分导致心脏收缩性改变。
