https://scholars.lib.ntu.edu.tw/handle/123456789/452642
標題: | Methylglyoxal in cells elicits a negative feedback loop entailing transglutaminase 2 and glyoxalase 1 | 作者: | Lee, Der-Yen GEEN-DONG CHANG |
關鍵字: | Glyoxalase 1; Methylglyoxal; Oxidative stress; Transglutaminase 2 | 公開日期: | 2014 | 卷: | 2 | 期: | 1 | 起(迄)頁: | 196 - 205 | 來源出版物: | Redox Biology | 摘要: | Glyoxalase 1 (GlxI) is the key enzyme that converts the highly reactive α-oxo-aldehydes into the corresponding α-hydroxy acids using l-glutathione as a cofactor. In our preliminary data, GlxI was identified as a substrate of transglutaminase 2 (TG2), a ubiquitous enzyme with multiple functions. According to the catalytic properties of TG2, protein cross-linking, polyamine conjugation, and/or deamidation are potential post-translational modifications. In this article, we have demonstrated that TG2 catalyzes either polyamine conjugation or deamidation to GlxI depending on the presence of polyamines or not. Deamidation leads to activation of GlxI while polyamine conjugation results in activation of GlxI as well as stabilization of GlxI against denaturation treatment. In cultured HeLa cells, methylglyoxal challenge causes increase in intracellular levels of reactive oxygen species (ROS) and calcium leading to TG2 activation and subsequent transamidation and activation of GlxI. The inhibition of TG2 significantly weakens the cell resistance to the methylglyoxal challenge. Thus, GlxI is a novel substrate of TG2 and is activated by TG2 in vitro and in cellulo. Exposure to methylglyoxal elicits a negative feedback loop entailing ROS, calcium, TG2 and GlxI, thus leading to attenuation of the increase in the methylglyoxal level. The results imply that cancer cells highly express TG2 or GlxI can endure the oxidative stress derived from higher glycolytic flux and may gain extra growth advantage from the aerobic glycolysis. ? 2014 The Authors. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/452642 https://www2.scopus.com/inward/record.uri?eid=2-s2.0-84893160083&doi=10.1016%2fj.redox.2013.12.024&partnerID=40&md5=f75c3f4a4de47be654b33f7131aaab8d |
ISSN: | 22132317 | DOI: | 10.1016/j.redox.2013.12.024 | SDG/關鍵字: | lactoylglutathione lyase; methylglyoxal; polyamine; protein glutamine gamma glutamyltransferase 2; reactive oxygen metabolite; calcium; methylglyoxal; calcium; GLO1 protein, human; guanine nucleotide binding protein; lactoylglutathione lyase; phenylglyoxal; protein glutamine gamma glutamyltransferase; protein glutamine gamma glutamyltransferase 2; reactive oxygen metabolite; aerobic glycolysis; article; attenuation; controlled study; deamination; enzyme activation; enzyme activity; enzyme denaturation; enzyme inhibition; enzyme mechanism; enzyme substrate; glycolysis; HeLa cell; human; human cell; in vitro study; negative feedback; oxidative stress; priority journal; protein cross linking; protein processing; aerobic metabolism; Article; catalysis; cell growth; conjugation; enzyme regulation; enzyme stability; HeLa cell line; protein protein interaction; drug effects; feedback system; metabolism; protein stability; Calcium; Feedback, Physiological; GTP-Binding Proteins; HeLa Cells; Humans; Lactoylglutathione Lyase; Phenylglyoxal; Polyamines; Protein Processing, Post-Translational; Protein Stability; Reactive Oxygen Species; Transglutaminases |
顯示於: | 生化科學研究所 |
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