Methylglyoxal production in vascular smooth muscle cells from different metabolic precursors
Methylglyoxal production in vascular smooth muscle cells from different metabolic precursors
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DOI：
10.1016/j.metabol.2008.04.014
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发表时间：
2008-09-01
影响因子：
9.8
通讯作者：
Wu, Lingyun
中科院分区：
文献类型：
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作者：
Dhar, Arti;Desai, Kaushik;Wu, Lingyun
甲基乙二醛(MG)是一种代谢副产物，与某些蛋白质反应生成不可逆的晚期糖基化终产物(AGEs)，并增加氧化应激，导致糖尿病、高血压和衰老的病理生理变化。虽然从葡萄糖中产生MG已经得到了很好的证明，但其他不同代谢途径的中间体对MG形成的贡献却知之甚少。我们的目的是测定和比较不同代谢前体对培养的大鼠主动脉血管平滑肌细胞(VSMCs)形成MG、MG诱导的AGE、N-epsilon-羧乙基赖氨酸(CEL)、诱导型一氧化氮合酶(NOS)、一氧化氮和过氧亚硝酸盐的影响。用高效液相色谱法测定MG水平，而亚硝酸盐+硝酸盐是一氧化氮产生的指标，过氧亚硝酸盐水平是用特定的检测试剂盒测定的。用免疫细胞化学方法检测CEL和NOS的表达。5、15和25 mmoL/L的D-葡萄糖果糖或氨基丙酮孵育3h后，VSMC的MG水平呈浓度依赖性增加。氨丙酮使MG水平高于基础值7倍，其次是果糖(3.9倍)、D-葡萄糖(3.5倍)、丙醇(2.8倍)和蔗糖(2.3倍)，每个前体与25 mmoL/L孵育3小时后。L葡萄糖、3-O-甲基葡萄糖和甘露醇对MG产量无影响。除L葡萄糖、3-O-甲基葡萄糖和甘露醇外，其余前体均能增加CEL。氨基丙酮、D-葡萄糖和果糖显著增加一氧化氮合酶、亚硝酸盐/硝酸盐和过氧亚硝酸盐水平。总而言之，氨基丙酮是VSMC产生MG最有效的前体，其次是果糖和D-葡萄糖。这可能对高果糖和蛋白质摄入量有重要影响。(C)2008 Elsevier Inc.保留所有权利。
Methylglyoxal (MG), a metabolic by-product, reacts with certain proteins to yield irreversible advanced glycation end products (AGEs) and increases oxidative stress that causes the pathophysiological changes in diabetes, hypertension, and aging. Although MG production from glucose has been well documented, the contribution of other intermediates of different metabolic pathways to MG formation is far less known. Our aim was to determine and compare the formation of MG, MG-induced AGE, N-epsilon-carboxyethyl-lysine (CEL), inducible nitric oxide synthase (NOS), nitric oxide, and peroxynitrite from different metabolic precursors in Cultured rat aortic vascular smooth muscle cells (VSMCs). High-performance liquid chromatography was used to determine MG levels, whereas nitrite + nitrate, indicators of nitric oxide production, and peroxynitrite levels were measured with specific assay kits. The CEL and NOS were detected using immunocytochemistry. There was a concentration-dependent increase in MG levels in VSMCs after 3-hour incubation with 5, 15, and 25 mmol/L of D-glucose fructose, or aminoacetone. Aminoacetone produced a 7-fold increase in MG levels above the basal value followed by fructose (3.9-fold), D-glucose (3.5-fold), acetol (2.8-fold), and sucrose (2.3-fold) after a 3-hour incubation with 25 mmol/L of each precursor. L-Glucose, 3-O-methylglucose, and mannitol had no effect on MG production. All precursors, except L-glucose, 3-O-methylglucose and mannitol, increased CEL. Aminoacetone, D-glucose, and fructose significantly increased NOS, nitrite/nitrate, and peroxynitrite levels. In conclusion, aminoacetone is the most potent precursor of MG production in VSMCs, followed by fructose and D-glucose. This could have important implications in relation to high dietary fructose and protein intake. (c) 2008 Elsevier Inc. All rights reserved.