title: Intracellular Accumulation of Methylglyoxal by Glyoxalase 1 Knock Down Alters Collagen Homoeostasis in L6 Myoblasts.
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.
authors.affiliation: Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universität Bochum, 32545 Bad Oeynhausen, Germany. bstratmann@hdz-nrw.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Stratmann
authors.affiliation: Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universität Bochum, 32545 Bad Oeynhausen, Germany. bgoldstein@hdz-nrw.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Goldstein
authors.affiliation: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK. P.J.Thornalley@warwick.ac.uk.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
authors.affiliation: Warwick Medical School, Clinical Sciences Research Laboratories, University of Warwick, University Hospital, Coventry CV2 2DX, UK. N.Rabbani@warwick.ac.uk.
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.affiliation: Herz- and Diabeteszentrum NRW, Diabeteszentrum, Ruhr Universität Bochum, 32545 Bad Oeynhausen, Germany. diethelm.tschoepe@rub.de.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Tschoepe
mesh_terms: D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats
chemical_list: D011765:Pyruvaldehyde; D003094:Collagen; D007791:Lactoylglutathione Lyase; D005947:Glucose
keywords: collagen; dicarbonyl proteome; glyoxalase 1; hyperglycemia; methylglyoxal