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Differential Effects of High Glucose and Methylglyoxal on Viability and Polyol Metabolism in Immortalized Adult Mouse Schwann Cells 高糖和甲基乙二醛对永生化成年小鼠雪旺细胞活力和多元醇代谢的差异影响
Pub Date : 2008-12-24 DOI: 10.2174/1876524600801010001
K. Sango, H. Yanagisawa, Koichi Kato, N. Kato, H. Hirooka, K. Watabe
Cultured Schwann cells under exposure to high glucose and methylglyoxal (MG) have been individually em- ployed for studying diabetic neuropathy; however, similarities and differences between these two culture models have not been studied. We investigated the effects of high glucose and MG on viability, polyol pathway activity, and expression of oxidative stress markers (4-hydroxy-2-nonenal (4HNE), acrolein (ACR), and hexanoyl lysine (HEL)) in immortalized adult mouse Schwann cells (IMS32 cell line) in culture. Western blot and immunocytochemical analyses revealed that ex- pression of aldose reductase (AR), 4HNE, ACR, and HEL in IMS32 was induced by exposure to both high glucose (30 mM) and MG (0.5 mM) for 48 h. Treatment with MG (0.1, 0.2, and 0.5 mM) induced cell death in a concentration- dependent manner, whereas high glucose environments (30 mM and 56 mM) did not impair cell viability. In contrast, in- tracellular sorbitol and fructose levels were significantly increased by high glucose, but not by MG. Taking these findings together, IMS32 cell line under high glucose conditions appears to be useful for studying oxidative stress in relation to the polyol pathway hyperactivity in diabetes. MG is capable of causing more detrimental damage to IMS32 than high glucose, but MG-induced upregulation of AR is unlikely to accelerate the polyol pathway activity.
暴露于高糖和甲基乙二醛(MG)下培养的雪旺细胞已被单独用于研究糖尿病神经病变;然而,这两种文化模式之间的异同尚未得到研究。我们研究了高糖和MG对培养的永生化成年小鼠雪旺细胞(IMS32细胞系)活力、多元醇途径活性和氧化应激标志物(4-羟基-2-壬烯醛(4HNE)、丙烯醛(ACR)和己醇赖氨酸(HEL))表达的影响。Western blot和免疫细胞化学分析显示,暴露于高糖(30 mM)和MG (0.5 mM) 48小时后,IMS32中醛糖还原酶(AR)、4HNE、ACR和HEL的表达均被诱导。MG(0.1、0.2和0.5 mM)以浓度依赖的方式诱导细胞死亡,而高糖环境(30 mM和56 mM)不损害细胞活力。相比之下,高葡萄糖显著增加了胞内山梨醇和果糖水平,而MG则没有。综上所述,高糖条件下的IMS32细胞系似乎有助于研究糖尿病多元醇通路过度活跃与氧化应激的关系。MG对IMS32的损害比高糖更严重,但MG诱导的AR上调不太可能加速多元醇途径的活性。
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引用次数: 13
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The Open Diabetes Journal
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