胰岛素刺激的NAD(P)H氧化酶活性增加培养的血管平滑肌细胞的迁移。
Insulin-stimulated NAD(P)H oxidase activity increases migration of cultured vascular smooth muscle cells.
作者信息
Yang Ming, Foster Estrella, Kahn Andrew M
机构信息
Division of Renal Diseases and Hypertension, Department of Internal Medicine, University of Texas Medical School, Houston, Texas 77030, USA.
出版信息
Am J Hypertens. 2005 Oct;18(10):1329-34. doi: 10.1016/j.amjhyper.2005.04.012.
BACKGROUND
We reported that insulin stimulates NAD(P)H oxidase activity but not migration of cultured rat vascular smooth muscle cells (VSMCs). Because angiotensin II (Ang II) increases NAD(P)H oxidase activity in these cells, we wished to determine whether insulin stimulates migration of Ang II-treated VSMCs by synergistically stimulating enzyme activity.
METHODS
Cultured rat VSMC superoxide anion (O2-) production, cyclic GMP production, and migration were measured by lucigenin luminescence, immunoassay, and wound closure rate, respectively. Nitric oxide (NO) scavenging was measured by inhibition of NO-induced fluorescence of 4-5-diaminofluorescin.
RESULTS
Insulin (1 nmol/L) did not affect and Ang II (100 nmol/L) stimulated VSMC migration by 65% (P < .05), but together stimulated it by 150% (P < .05 versus Ang II) by a mechanism inhibited by the NAD(P)H oxidase inhibitors, diphenyleneiodonium (DPI) or gp91ds-tat. Insulin and Ang II stimulated O2- production by 34% and 35%, respectively (both P < .05), but together synergistically stimulated it by 143% (P < .05 versus insulin or Ang II) in a DPI or gp91ds-tat-sensitive manner. Neither insulin nor Ang II measurably affected NO scavenging, but together reduced NO availability by 46% in a DPI-sensitive manner (P < .05) and significantly inhibited NO-stimulated cyclic GMP production.
CONCLUSIONS
Insulin synergestically stimulates NAD(P)H oxidase activity in Ang II-treated cultured rat VSMCs causing increased migration.
背景
我们曾报道胰岛素可刺激烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）氧化酶活性，但不影响培养的大鼠血管平滑肌细胞（VSMC）的迁移。由于血管紧张素II（Ang II）可增加这些细胞中的NAD(P)H氧化酶活性，我们希望确定胰岛素是否通过协同刺激酶活性来刺激经Ang II处理的VSMC迁移。
方法
分别通过光泽精发光、免疫测定和伤口闭合率来测量培养的大鼠VSMC超氧阴离子（O2-）生成、环磷酸鸟苷（cGMP）生成和迁移。通过抑制一氧化氮（NO）诱导的4,5-二氨基荧光素荧光来测量NO清除。
结果
胰岛素（1 nmol/L）不影响VSMC迁移，而Ang II（100 nmol/L）可使VSMC迁移增加65%（P < 0.05），但二者共同作用时可使迁移增加150%（与Ang II相比，P < 0.05），其机制可被NAD(P)H氧化酶抑制剂二苯碘鎓（DPI）或gp91ds-tat抑制。胰岛素和Ang II分别使O2-生成增加34%和35%（均为P < 0.05），但二者共同作用时以DPI或gp91ds-tat敏感的方式协同使O2-生成增加143%（与胰岛素或Ang II相比，P < 0.05）。胰岛素和Ang II均未显著影响NO清除，但二者共同作用时以DPI敏感的方式使NO可用性降低46%（P < 0.05），并显著抑制NO刺激的cGMP生成。
结论
胰岛素协同刺激经Ang II处理的培养大鼠VSMC中的NAD(P)H氧化酶活性，导致迁移增加。
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