Loss of glyoxalase 2 alters the glucose metabolism in zebrafish.

Autor:	Tabler CT; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Lodd E; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Bennewitz K; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Middel CS; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Erben V; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Ott H; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Poth T; CMCP - Center for Model System and Comparative Pathology, Institute of Pathology, Heidelberg University Hospital, 69120, Heidelberg, Germany., Fleming T; Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120, Heidelberg, Germany., Morgenstern J; Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120, Heidelberg, Germany., Hausser I; Institute of Pathology IPH, EM Lab, Heidelberg University Hospital, 69120, Heidelberg, Germany., Sticht C; NGS Core Facility, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany., Poschet G; Metabolomics Core Technology Platform, Centre for Organismal Studies, Heidelberg University, 69120, Heidelberg, Germany., Szendroedi J; Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120, Heidelberg, Germany., Nawroth PP; Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, 69120, Heidelberg, Germany., Kroll J; Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany. Electronic address: jens.kroll@medma.uni-heidelberg.de.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2023 Feb; Vol. 59, pp. 102576. Date of Electronic Publication: 2022 Dec 14.
DOI:	10.1016/j.redox.2022.102576
Abstrakt:	Glyoxalase 2 is the second enzyme of the glyoxalase system, catalyzing the detoxification of methylglyoxal to d-lactate via SD-Lactoylglutathione. Recent in vitro studies have suggested Glo2 as a regulator of glycolysis, but if Glo2 regulates glucose homeostasis and related organ specific functions in vivo has not yet been evaluated. Therefore, a CRISPR-Cas9 knockout of glo2 in zebrafish was created and analyzed. Consistent with its function in methylglyoxal detoxification, SD-Lactoylglutathione, but not methylglyoxal accumulated in glo2 -/- larvae, without altering the glutathione metabolism or affecting longevity. Adult glo2 -/- livers displayed a reduced hexose concentration and a reduced postprandial P70-S6 kinase activation, but upstream postprandial AKT phosphorylation remained unchanged. In contrast, glo2 -/- skeletal muscle remained metabolically intact, possibly compensating for the dysfunctional liver through increased glucose uptake and glycolytic activity. glo2 -/- zebrafish maintained euglycemia and showed no damage of the retinal vasculature, kidney, liver and skeletal muscle. In conclusion, the data identified Glo2 as a regulator of cellular energy metabolism in liver and skeletal muscle, but the redox state and reactive metabolite accumulation were not affected by the loss of Glo2. Competing Interests: Declaration of competing interest Declarations of interest: none. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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