Lindsey S H, Tribe R M, Songu-Mize E
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, P7-1, New Orleans, LA 70112, United States.
Life Sci. 2008 Jul 4;83(1-2):29-34. doi: 10.1016/j.lfs.2008.04.013. Epub 2008 May 6.
We investigated whether cyclic stretch affects TRPC4 or TRPC6 expression and calcium mobilization in cultured vascular smooth muscle cells. In aortic and mesenteric smooth muscle cells isolated from male Sprague-Dawley rats, TRPC4 expression was decreased after 5 h stretch and remained suppressed through 24 h stretch. After removal of the stretch stimulus, TRPC4 expression recovered within 2 h. Stretch did not affect TRPC6 expression. Stretch also decreased capacitative calcium entry, while agonist-induced calcium influx was increased. Similar results were obtained in primary aortic smooth muscle cells. TRPC4 mRNA levels were not decreased in response to mechanical strain. TRPC4 downregulation was also achieved by increasing extracellular calcium and was attenuated by gadolinium and MG132, suggesting that TRPC4 protein is regulated by intracellular calcium concentration and/or the ubiquitin-proteasome pathway. These data suggest that stretch-induced downregulation of TRPC4 protein expression and capacitative calcium entry may be a protective mechanism to offset stretch-induced increases in intracellular calcium.
我们研究了周期性牵张是否会影响培养的血管平滑肌细胞中TRPC4或TRPC6的表达以及钙动员。在从雄性Sprague-Dawley大鼠分离的主动脉和肠系膜平滑肌细胞中，TRPC4表达在牵张5小时后降低，并在24小时牵张过程中持续受到抑制。去除牵张刺激后，TRPC4表达在2小时内恢复。牵张不影响TRPC6的表达。牵张还减少了储存性钙内流，而激动剂诱导的钙内流增加。在原代主动脉平滑肌细胞中也获得了类似的结果。TRPC4 mRNA水平对机械应变无降低反应。通过增加细胞外钙也可实现TRPC4的下调，且钆和MG132可减弱这种下调，这表明TRPC4蛋白受细胞内钙浓度和/或泛素-蛋白酶体途径调控。这些数据表明，牵张诱导的TRPC4蛋白表达下调和储存性钙内流可能是一种保护机制，以抵消牵张诱导的细胞内钙增加。
