Carnosine catalyzes the formation of the oligo/polymeric products of methylglyoxal

• Verfasst von: Weigand, Tim [VerfasserIn]
• Verfasst von: Singler, Benjamin [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Thiel, Christian [VerfasserIn]
• Verfasst von: Garbade, Sven [VerfasserIn]
• Verfasst von: Wagner, Andreas H. [VerfasserIn]
• Verfasst von: Hecker, Markus [VerfasserIn]
• Verfasst von: Yard, Benito A. [VerfasserIn]
• Verfasst von: Schmitt, Claus P. [VerfasserIn]
• Verfasst von: Peters, Verena [VerfasserIn]
• Titel: Carnosine catalyzes the formation of the oligo/polymeric products of methylglyoxal
• Mitwirkende: Amberger, Albert
• Verf.angabe: Tim Weigand, Benjamin Singler, Thomas Fleming, Peter Nawroth, Karel D. Klika, Christian Thiel, Hans Baelde, Sven F. Garbade, Andreas H. Wagner, Markus Hecker, Benito A. Yard, Albert Amberger, Johannes Zschocke, Claus P. Schmitt, Verena Peters
• E-Jahr: 2018
• Jahr: April 05, 2018
• Umfang: 14 S.
• Fussnoten: Gesehen am 03.07.2019
• Titel Quelle: Enthalten in: Cellular physiology and biochemistry
• Ort Quelle: Düsseldorf : Cell Physiol Biochem Press GmbH & Co KG, 1991
• Jahr Quelle: 2018
• Band/Heft Quelle: 46(2018), 2, Seite 713-726
• ISSN Quelle: 1421-9778
• DOI: doi:10.1159/000488727
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Animals
• Sach-SW: Anserine
• Sach-SW: Carnosine
• Sach-SW: Cell Line
• Sach-SW: Cell Survival
• Sach-SW: Chromatography, High Pressure Liquid
• Sach-SW: Diabetic nephropathy
• Sach-SW: Glutathione
• Sach-SW: Glutathione Peroxidase
• Sach-SW: Glycation End Products, Advanced
• Sach-SW: Humans
• Sach-SW: Membrane Glycoproteins
• Sach-SW: Membrane Transport Proteins
• Sach-SW: Methylglyoxal
• Sach-SW: Mice
• Sach-SW: Oxidative Stress
• Sach-SW: Peptide Transporter 1
• Sach-SW: Podocytes
• Sach-SW: Polymers
• Sach-SW: Pyruvaldehyde
• Sach-SW: Renal cells
• Sach-SW: Serum Albumin
• Sach-SW: Superoxide Dismutase
• Sach-SW: Symporters
• Sach-SW: Taurine transporter
• K10plus-PPN: 1668447282

Abstract

BACKGROUND/AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo. - METHODS: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC. - RESULTS: In vitro, carnosine and anserine dose-dependently reduced N-carboxyethyl lysine (CEL) and advanced glycation end products (AGEs) formation. NMR studies revealed the formation of oligo/polymeric products of MG catalyzed by carnosine or anserine. MG toxicity (0.3-1 mM) was dose-dependent for podocytes, tubular and mesangial cells whereas low MG levels (0.2 mM) resulted in increased cell viability in podocytes (143±13%, p<0.001) and tubular cells (129±3%, p<0.001). Incubation with carnosine/anserine did not reduce MG-induced toxicity, independent of incubation times and across large ranges of MG to carnosine/anserine ratios. Cellular carnosine uptake was low (<0.1% in 20 hours) and cellular carnosine concentrations remained unaffected. The putative carnosine transporter PHT1 along with the taurine transporter (TauT) was expressed in all cell types while PEPT1, PEPT2 and PHT2, also belonging to the proton-coupled oligopeptide transporter (POT) family, were only expressed in tubular cells. - CONCLUSION: While carnosine and anserine catalyze the formation of MG oligo/polymers, the molar ratios required for protection from MG-induced cellular toxicity are not achievable in renal cells. The effect of carnosine in vivo, to mitigate diabetic nephropathy may therefore be independent upon its ability to scavenge MG and/or carnosine is mainly acting extracellularly.