首页> 外文期刊>Endothelium: Journal of endothelial cell research >Regulation of the glyoxalase pathway in human brain microvascular endothelium: effects of troglitazone and tertiary butylhydroperoxide.
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Regulation of the glyoxalase pathway in human brain microvascular endothelium: effects of troglitazone and tertiary butylhydroperoxide.

机译:人脑微血管内皮中乙二醛酶途径的调节:曲格列酮和叔丁基氢过氧化物的作用。

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摘要

The glyoxalase system, comprised of glyoxalase-I and glyoxalase-II with glutathione as the cofactor, plays an important role in the detoxification of methylglyoxal and other alpha-oxo-aldehydes. Such aldehydes, which increase with hyperglycemia, give rise to advanced glycation end products. The objective of this research was to examine the glyoxalase system in human cerebromicrovascular cells. The hypothesis tested was that this pathway would be regulated by phase 2 enzyme inducers such as t-butylhydroquinone and modulated by the insulin-sensitizing drug troglitazone. Human cerebromicrovascular endothelial cells were cultured and exposed to varying concentrations of t-butylhydroquinone or troglitazone. The activity of glyoxylase-I in human endothelial cells was similar to the activity present in hepatocytes. The phase 2 enzyme inducer t-butylhydroquinone had no effect on the glyoxalase enzymes activities but significantly increased glutathione levels and glutathione reductase activity, indicating that phase 2 enzyme inducers might promote alpha-oxo-aldehyde scavenging. Troglitazone decreased the activities of glyoxalase-I and -II and decreased glyoxalase-I mRNA. Troglitazone had no effect on glutathione levels or on the activity of glutathione reductase or glutathione peroxidase. We conclude that phase 2 enzyme inducers may promote scavenging of alpha-oxoaldehydes in endothelial cells.
机译:由乙二醛酶I和乙二醛酶II与谷胱甘肽作为辅因子组成的乙二醛酶系统在甲基乙二醛和其他α-氧代醛的解毒中起重要作用。随着高血糖而增加的此类醛产生高级糖基化终产物。这项研究的目的是检查人脑微血管细胞中的乙二醛酶系统。测试的假设是该途径将受2期酶诱导剂(例如叔丁基对苯二酚)的调节,并受到胰岛素敏感性药物曲格列酮的调节。培养人脑微血管内皮细胞,并使其暴露于不同浓度的叔丁基对苯二酚或曲格列酮。人内皮细胞中乙醛酸酶-1的活性类似于肝细胞中存在的活性。 2期酶诱导剂叔丁基对苯二酚对乙二醛酶活性没有影响,但显着增加了谷胱甘肽水平和谷胱甘肽还原酶活性,表明2期酶诱导剂可能会促进α-氧代醛清除。曲格列酮降低了乙二醛酶-I和-II的活性,并降低了乙二醛酶-I的mRNA。曲格列酮对谷胱甘肽水平或谷胱甘肽还原酶或谷胱甘肽过氧化物酶的活性没有影响。我们得出结论,2期酶诱导剂可能会促进内皮细胞中α-氧醛的清除。

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