Wu Lingyun, Juurlink Bernhard H J
Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Hypertension. 2002 Mar 1;39(3):809-14. doi: 10.1161/hy0302.105207.
Methylglyoxal can yield advanced glycation end products via nonenzymatic glycation of proteins. Whether methylglyoxal contributes to the pathogenesis of hypertension has not been clear. The aim of the present study was to investigate whether the levels of methylglyoxal and methylglyoxal-induced advanced glycation end products were enhanced and whether methylglyoxal increased oxidative stress, activated nuclear factor-kappaB (NF-kappaB), and increased intracellular adhesion molecule-1 (ICAM-1) content in vascular smooth muscle cells from spontaneously hypertensive rats. Basal cellular levels of methylglyoxal and advanced glycation end products were more than 2-fold higher (P<0.05) in cells from hypertensive rats than from normotensive Wistar-Kyoto rats. This correlated with levels of oxidative stress and oxidized glutathione that were significantly higher in cells from hypertensive rats, whereas levels of glutathione and activities of glutathione reductase and glutathione peroxidase were significantly lower. Basal levels of nuclearly localized NF-kappaB p65 and ICAM-1 protein expression were higher in cells from hypertensive rats than from normotensive rats. Addition of exogenous methylglyoxal to the cultures induced a greater increase in oxidative stress and advanced glycation end products in cells from hypertensive rats compared with normotensive rats and significantly decreased the activities of glutathione reductase and glutathione peroxidase in cells of both rat strains. Methylglyoxal activated NF-kappaB p65 and increased ICAM-1 expression in hypertensive cells, which was inhibited by N-acetylcysteine. Our study demonstrates an elevated methylglyoxal level and advanced glycation end products in cells from hypertensive rats, and methylglyoxal increases oxidative stress, activates NF-kappaB, and enhances ICAM-1 expression. Our findings suggest that that elevated methylglyoxal and associated oxidative stress possibly contribute to the pathogenesis of hypertension.
甲基乙二醛可通过蛋白质的非酶糖基化作用产生晚期糖基化终末产物。甲基乙二醛是否参与高血压的发病机制尚不清楚。本研究的目的是调查自发性高血压大鼠血管平滑肌细胞中甲基乙二醛及其诱导的晚期糖基化终末产物水平是否升高，以及甲基乙二醛是否会增加氧化应激、激活核因子-κB（NF-κB）并增加细胞间黏附分子-1（ICAM-1）的含量。高血压大鼠细胞中甲基乙二醛和晚期糖基化终末产物的基础细胞水平比正常血压的Wistar-Kyoto大鼠细胞高2倍以上（P<0.05）。这与高血压大鼠细胞中显著更高的氧化应激水平和氧化型谷胱甘肽水平相关，而谷胱甘肽水平以及谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性则显著更低。高血压大鼠细胞中核定位的NF-κB p65基础水平和ICAM-1蛋白表达高于正常血压大鼠细胞。与正常血压大鼠相比，向培养物中添加外源性甲基乙二醛可使高血压大鼠细胞中的氧化应激和晚期糖基化终末产物增加得更多，并显著降低两种大鼠品系细胞中谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性。甲基乙二醛激活高血压细胞中的NF-κB p65并增加ICAM-1表达，而N-乙酰半胱氨酸可抑制这一作用。我们的研究表明，高血压大鼠细胞中甲基乙二醛水平和晚期糖基化终末产物升高，并且甲基乙二醛会增加氧化应激、激活NF-κB并增强ICAM-1表达。我们的研究结果表明，甲基乙二醛水平升高及相关氧化应激可能参与高血压的发病机制。
