Takahashi Yoichiro, Watanabe Hiroyuki, Murakami Manabu, Ono Kyoichi, Munehisa Yoshiko, Koyama Takashi, Nobori Kiyoshi, Iijima Toshihiko, Ito Hiroshi
Second Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Biochem Biophys Res Commun. 2007 Oct 5;361(4):934-40. doi: 10.1016/j.bbrc.2007.07.096. Epub 2007 Jul 26.
We investigated the functional role of STIM1, a Ca(2+) sensor in the endoplasmic reticulum (ER) that regulates store-operated Ca(2+) entry (SOCE), in vascular smooth muscle cells (VSMCs). STIM1 was mainly localized at the ER and plasma membrane. The knockdown of STIM1 expression by small interfering (si) RNA drastically decreased SOCE. In contrast, an EF-hand mutant of STIM1, STIM1(E87A), produced a marked increase in SOCE, which was abolished by co-transfection with siRNA to transient receptor potential canonical 1 (TRPC1). In addition, transfection with siRNA against STIM1 suppressed phosphorylation of cAMP-responsive element binding protein (CREB) and cell growth. These results suggest that STIM1 is an essential component of SOCE and that it is involved in VSMC proliferation.
我们研究了基质相互作用分子1（STIM1）在血管平滑肌细胞（VSMC）中的功能作用，STIM1是内质网（ER）中的一种Ca(2+)传感器，可调节钙库操纵的Ca(2+)内流（SOCE）。STIM1主要定位于内质网和质膜。通过小干扰（si）RNA敲低STIM1表达可显著降低SOCE。相反，STIM1的EF手型突变体STIM1（E87A）可使SOCE显著增加，而与瞬时受体电位香草酸亚型1（TRPC1）的siRNA共转染可消除这种增加。此外，用针对STIM1的siRNA转染可抑制环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化和细胞生长。这些结果表明，STIM1是SOCE的重要组成部分，并且参与VSMC增殖。
