生理系统中乙二醛和甲基乙二醛对蛋白质和核苷酸的损伤——在衰老和疾病中的作用
Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems--role in ageing and disease.
作者信息
Thornalley Paul J
机构信息
Protein Damage and Systems Biology Research Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry, UK.
出版信息
Drug Metabol Drug Interact. 2008;23(1-2):125-50. doi: 10.1515/dmdi.2008.23.1-2.125.
Abstract
Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal--physiological substrates of glyoxalase 1--is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these alpha-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Györgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate that glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process--implying a role in cell signalling, ageing and disease.
摘要
乙二醛和甲基乙二醛（乙二醛酶1的生理底物）对蛋白质、核苷酸和碱性磷脂的糖基化作用可能会对蛋白质组、基因组和脂质组造成损害。乙二醛酶1可抑制这些α-氧代醛代谢物引起的糖基化作用，因此是对抗糖基化的酶防御机制的一部分。阿尔伯特·圣捷尔吉率先并努力理解甲基乙二醛和乙二醛酶系统的生理功能。我们现在认识到，乙二醛酶1可防止蛋白质组、基因组和脂质组发生二羰基修饰。最新研究表明，这一过程存在功能修饰，意味着其在细胞信号传导、衰老和疾病中发挥作用。
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本文引用的文献
1
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Kidney Int. 2007 Nov;72(9):1113-21. doi: 10.1038/sj.ki.5002513. Epub 2007 Aug 29.
2
2-DE analysis of a new human cell line EM-G3 derived from breast cancer progenitor cells and comparison with normal mammary epithelial cells.对源自乳腺癌祖细胞的新型人类细胞系EM-G3进行双向电泳分析，并与正常乳腺上皮细胞进行比较。
Proteomics. 2007 May;7(9):1549-59. doi: 10.1002/pmic.200600907.
3
Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r).小鼠第17号染色体上碳水化合物和总能量摄入的数量性状基因座：同源近交系确认及候选基因分析（Glo1、Glp1r）
Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R207-16. doi: 10.1152/ajpregu.00491.2006. Epub 2006 Aug 31.
4
Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification.高血糖状态下内皮细胞中双羰基代谢增加，通过RGD和GFOGER基序修饰诱导失巢凋亡并损害血管生成。
Diabetes. 2006 Jul;55(7):1961-9. doi: 10.2337/db05-1634.
5
Methylglyoxal impairs the insulin signaling pathways independently of the formation of intracellular reactive oxygen species.甲基乙二醛独立于细胞内活性氧的形成而损害胰岛素信号通路。
Diabetes. 2006 May;55(5):1289-99. doi: 10.2337/db05-0857.
6
Unease on the role of glyoxalase 1 in high-anxiety-related behaviour.对乙二醛酶1在高焦虑相关行为中作用的担忧。
Trends Mol Med. 2006 May;12(5):195-9. doi: 10.1016/j.molmed.2006.03.004. Epub 2006 Apr 17.
7
Methylglyoxal downregulates Raf-1 protein through a ubiquitination-mediated mechanism.甲基乙二醛通过泛素化介导的机制下调Raf-1蛋白。
Int J Biochem Cell Biol. 2006;38(7):1084-91. doi: 10.1016/j.biocel.2005.10.019. Epub 2005 Dec 1.
8
Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice.乙二醛酶1和谷胱甘肽还原酶1调节小鼠的焦虑情绪。
Nature. 2005 Dec 1;438(7068):662-6. doi: 10.1038/nature04250. Epub 2005 Oct 23.
9
Glycation free adduct accumulation in renal disease: the new AGE.肾脏疾病中无糖化加合物的积累：新的晚期糖基化终末产物
Pediatr Nephrol. 2005 Nov;20(11):1515-22. doi: 10.1007/s00467-005-2011-9. Epub 2005 Aug 24.
10
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