High glucose enhances inducible nitric oxide synthase expression. Role of protein kinase C-βII
High glucose enhances inducible nitric oxide synthase expression. Role of protein kinase C-βII
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DOI：
10.1016/j.ejphar.2006.03.052
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发表时间：
2006-05-24
影响因子：
5
通讯作者：
Salaices, Mercedes
中科院分区：
文献类型：
--
作者：
Pacheco, Maria E.;Beltran, Amada;Salaices, Mercedes
目的是确定高葡萄糖水平是否会干扰正常血压 Wistar京都大鼠和自发性高血压大鼠中白细胞介素 1 p 刺激的血管平滑肌细胞中一氧化氮 (NO) 的产生和诱导型一氧化氮合酶 (iNOS) 蛋白的表达。将细胞与正常 (5.5 mM) 或高 (22 MM) D-葡萄糖一起孵育 72 小时，并与白介素-1β (10 ng/ml) 一起孵育最后 24 小时。高葡萄糖会增加血压正常大鼠细胞中的亚硝酸盐水平、iNOS 表达和蛋白激酶 C 活性，但对高血压大鼠细胞没有影响。蛋白激酶 C-β II 的选择性抑制剂 5,21:12,17-dimetheno-18H-二苯并[i,o]吡咯并[3,4-1] [1,8]diacyclohexadecine-18,20 (19H)-dione 消除了高葡萄糖对亚硝酸盐生成和 iNOS 表达的影响， 8-[(二甲氨基)-甲基]6,7,8,9,10,11-六氢-单甲磺酸酯(LY379196, 30 nM)。 Calphostin C (1 mu M) 和 LY379196 (10 M) 仅在用两种培养基处理的正常血压大鼠的细胞中降低亚硝酸盐水平和 iNOS 表达。这些结果表明，高葡萄糖通过激活蛋白激酶 C-β II 来增加诱导型一氧化氮合酶的诱导和随后的 NO 产生；这种机制似乎在高血压中发生了改变。 (c) 2006 Elsevier B.V. 保留所有权利。
The aim was to determine whether high glucose levels interfere with nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression in interleukin-1 p-stimulated vascular smooth muscle cells from normotensive Wistar Kyoto and spontaneously hypertensive rats. Cells were incubated with either normal (5.5 mM) or high (22 MM) D-glucose for 72 h and with interleukin- 1 beta (10 ng/ml) for the last 24 h. High glucose increased nitrite levels, iNOS expression and protein kinase C activity in cells from normotensive rats and had no effect in cells from hypertensive rats. High glucose effects on nitrite production and iNOS expression was abolished by the selective inhibitor for the protein kinase C-beta II, 5,21:12,17-dimetheno-18H-dibenzo[i,o]pyrrolo[3,4-1] [1,8]diacyclohexadecine-18,20 (19H)-dione, 8-[(dimethylamino)-methyl]6,7,8,9,10,11-hexahydro-monomethanesulfonate (LY379196, 30 nM). Calphostin C (1 mu M) and LY379196 (10 M) reduced nitrite levels and iNOS expression only in cells from normotensive rats treated with both media. These results suggest that high glucose increases inducible nitric oxide synthase induction and subsequent NO production by activating the protein kinase C-beta II; this mechanism seems to be altered in hypertension. (c) 2006 Elsevier B.V. All rights reserved.