Canonical Transient Receptor Potential Channels Expression Is Elevated in a Porcine Model of Metabolic Syndrome
Canonical Transient Receptor Potential Channels Expression Is Elevated in a Porcine Model of Metabolic Syndrome
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DOI：
10.1210/me.2008-0350
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发表时间：
2009-05-01
影响因子：
--
通讯作者：
Obukhov, Alexander G.
中科院分区：
文献类型：
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作者：
Hu, Guoqing;Oboukhova, Elena A.;Obukhov, Alexander G.
代谢综合征中血浆肾上腺素和心率升高，表明肾上腺髓质的儿茶酚胺分泌增加。规范瞬时受体电位 (TRPC) 通道参与介导激素诱导的 Ca2+ 流入和肾上腺髓质嗜铬细胞中儿茶酚胺的分泌。我们研究了猪肾上腺髓质中 TRPC 的表达模式，并研究了糖尿病前期代谢综合征 Ossabaw 小型猪中肾上腺 TRPC 表达是否发生改变。我们结合使用了分子生物学、生化和荧光成像技术。我们确定了猪 TRPC1 和 TRPC3-7 通道的序列。我们发现猪肾上腺髓质主要表达 TRPC1、TRPC5 和 TRPC6 转录本。这些 TRPC 的表达水平在患有代谢综合征的猪的肾上腺髓质中显着升高。有趣的是，相邻肾上腺皮质内源性分泌的醛固酮增加了从代谢综合征分离的肾上腺嗜铬细胞中 TRPC1、TRPC5 和 TRPC6 的表达，但在对照猪中则不然。螺内酯是一种盐皮质激素受体阻滞剂，可抑制醛固酮的作用。地塞米松还增加了代谢综合征嗜铬细胞中 TRPC5 的表达。激素诱导的二价阳离子流入的幅度与肾上腺嗜铬细胞中 TRPC 表达水平相关。与对照组相比，代谢综合征肾上腺髓质中的 Orai1/Stim1 蛋白表达没有显着改变。我们认为，在代谢综合征中，异常升高的肾上腺 TRPC 表达可能是血浆肾上腺素和心率增加的基础。血浆儿茶酚胺过量和心率加快是心血管疾病的危险因素。因此，TRPC 是对抗心血管疾病的潜在治疗靶点。 （分子内分泌学23：689-699，2009）
Plasma epinephrine and heart rate are elevated in metabolic syndrome, suggesting enhanced catecholamine secretion from the adrenal medulla. Canonical transient receptor potential (TRPC) channels are implicated in mediating hormone-induced Ca2+ influx and catecholamine secretion in adrenomedullary chromaffin cells. We studied the pattern of TRPC expression in the pig adrenal medulla and investigated whether adrenal TRPC expression is altered in prediabetic metabolic syndrome Ossabaw miniature pigs. We used a combination of molecular biological, biochemical, and fluorescence imaging techniques. We determined the sequence of pig TRPC1 and TRPC3-7 channels. We found that the pig adrenal medulla expressed predominantly TRPC1, TRPC5, and TRPC6 transcripts. The expression level of these TRPCs was significantly elevated in the adrenal medulla from pigs with metabolic syndrome. Interestingly, aldosterone, which is endogenously secreted in the adjacent adrenal cortex, increased TRPC1, TRPC5, and TRPC6 expression in adrenal chromaffin cells isolated from metabolic syndrome but not control pigs. Spironolactone, a blocker of mineralocorticoid receptors, inhibited the aldosterone effect. Dexamethasone also increased TRPC5 expression in metabolic syndrome chromaffin cells. The amplitude of hormone-induced divalent cation influx correlated with the level of TRPC expression in adrenal chromaffin cells. Orai1/Stim1 protein expression was not significantly altered in the metabolic syndrome adrenal medulla when compared with the control. We propose that in metabolic syndrome, abnormally elevated adrenal TRPC expression may underlie increased plasma epinephrine and heart rate. The excess of plasma catecholamines and increased heart rate are risk factors for cardiovascular disease. Thus, TRPCs are potential therapeutic targets in the fight against cardiovascular disease. (Molecular Endocrinology 23: 689-699, 2009)