Intracellular Accumulation of Methylglyoxal by Glyoxalase 1 Knock Down Alters Collagen Homoeostasis in L6 Myoblasts

乙二醛酶 1 敲低导致甲基乙二醛在细胞内积累,从而改变 L6 成肌细胞中的胶原稳态

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作者:Bernd Stratmann, Bernhard Goldstein, Paul J Thornalley, Naila Rabbani, Diethelm Tschoepe

Abstract

Hyperglycemia results in accumulation of the reactive dicarbonyl methylglyoxal (MG). Methylglyoxal is detoxified by the glyoxalase system (glyoxalase 1 and 2). The influence of glyoxalase 1 knockdown on expression of collagens 1, 3, 4, and 5 in L6 myoblasts under hyperglycemic conditions was investigated. Increased biosynthesis of collagens 1, 3, 4, and 5 was detected at mRNA-level following knockdown of glyoxalase 1 (GLO1). At the protein level a significant elevation of the concentration of collagen 1 and 4 was shown, whereas no increase of collagen 5 and a non-significant increase in collagen 3 were detectable. These results could partially explain MG-induced changes in the extracellular matrix (ECM) which account for increased fibrosis and impaired function in myocytes. The mechanisms by which reactive glucose metabolites influence ECM composition deserve further investigation.

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