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

Int J Mol Sci. 2017 Feb 23;18(3):480. doi: 10.3390/ijms18030480.

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.

Keywords: collagen; dicarbonyl proteome; glyoxalase 1; hyperglycemia; methylglyoxal.

MeSH terms

  • Animals
  • Cell Line
  • Collagen / metabolism*
  • Extracellular Matrix / metabolism
  • Glucose / metabolism
  • Homeostasis*
  • Lactoylglutathione Lyase / genetics
  • Lactoylglutathione Lyase / metabolism*
  • Myoblasts / metabolism*
  • Pyruvaldehyde / metabolism*
  • Rats

Substances

  • Pyruvaldehyde
  • Collagen
  • Lactoylglutathione Lyase
  • Glucose