Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal - PubMed (original) (raw)

doi: 10.1159/000488727. Epub 2018 Mar 29.

Benjamin Singler 1, Thomas Fleming 2, Peter Nawroth 2 3 4, Karel D Klika 5, Christian Thiel 1, Hans Baelde 6, Sven F Garbade 1, Andreas H Wagner 7, Markus Hecker 7, Benito A Yard 8, Albert Amberger 9, Johannes Zschocke 9, Claus P Schmitt 1, Verena Peters 1

Affiliations

• PMID: 29621776
• DOI: 10.1159/000488727

Free article

Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal

Tim Weigand et al. Cell Physiol Biochem. 2018.

Free article

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.

Keywords: Anserine; Carnosine; Diabetic nephropathy; Methylglyoxal; Renal cells; Taurine transporter.

© 2018 The Author(s). Published by S. Karger AG, Basel.

PubMed Disclaimer

Similar articles

• The proton-coupled oligopeptide transporters PEPT2, PHT1 and PHT2 mediate the uptake of carnosine in glioblastoma cells.
  Oppermann H, Heinrich M, Birkemeyer C, Meixensberger J, Gaunitz F. Oppermann H, et al. Amino Acids. 2019 Jul;51(7):999-1008. doi: 10.1007/s00726-019-02739-w. Epub 2019 May 9. Amino Acids. 2019. PMID: 31073693
• Intrinsic carnosine metabolism in the human kidney.
  Peters V, Klessens CQ, Baelde HJ, Singler B, Veraar KA, Zutinic A, Drozak J, Zschocke J, Schmitt CP, de Heer E. Peters V, et al. Amino Acids. 2015 Dec;47(12):2541-50. doi: 10.1007/s00726-015-2045-7. Epub 2015 Jul 24. Amino Acids. 2015. PMID: 26206726 Free PMC article.
• The bioactive dipeptide anserine is transported by human proton-coupled peptide transporters.
  Geissler S, Zwarg M, Knütter I, Markwardt F, Brandsch M. Geissler S, et al. FEBS J. 2010 Feb;277(3):790-5. doi: 10.1111/j.1742-4658.2009.07528.x. Epub 2010 Jan 8. FEBS J. 2010. PMID: 20067523
• The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance.
  Boldyrev AA, Severin SE. Boldyrev AA, et al. Adv Enzyme Regul. 1990;30:175-94. doi: 10.1016/0065-2571(90)90017-v. Adv Enzyme Regul. 1990. PMID: 2206021 Review.
• [Discovery of carnosine and anserine. Some of their properties].
  Severin SE. Severin SE. Biokhimiia. 1992 Sep;57(9):1285-95. Biokhimiia. 1992. PMID: 1467348 Review. Russian.

Cited by

• Diabetes and Pancreatic Cancer-A Dangerous Liaison Relying on Carbonyl Stress.
  Menini S, Iacobini C, Vitale M, Pesce C, Pugliese G. Menini S, et al. Cancers (Basel). 2021 Jan 16;13(2):313. doi: 10.3390/cancers13020313. Cancers (Basel). 2021. PMID: 33467038 Free PMC article. Review.
• Methylglyoxal induces p53 activation and inhibits mTORC1 in human umbilical vein endothelial cells.
  Zhang X, Rodriguez-Niño A, Pastene DO, Pallavi P, van den Born J, Bakker SJL, Krämer BK, Yard BA. Zhang X, et al. Sci Rep. 2021 Apr 13;11(1):8004. doi: 10.1038/s41598-021-87561-9. Sci Rep. 2021. PMID: 33850227 Free PMC article.
• The protective role of carnosine against type 2 diabetes-induced cognitive impairment.
  Wang Q, Tripodi N, Valiukas Z, Bell SM, Majid A, de Courten B, Apostolopoulos V, Feehan J. Wang Q, et al. Food Sci Nutr. 2024 Mar 12;12(6):3819-3833. doi: 10.1002/fsn3.4077. eCollection 2024 Jun. Food Sci Nutr. 2024. PMID: 38873448 Free PMC article. Review.
• Carnosinase-1 Knock-Out Reduces Kidney Fibrosis in Type-1 Diabetic Mice on High Fat Diet.
  Pfeffer T, Wetzel C, Kirschner P, Bartosova M, Poth T, Schwab C, Poschet G, Zemva J, Bulkescher R, Damgov I, Thiel C, Garbade SF, Klingbeil K, Peters V, Schmitt CP. Pfeffer T, et al. Antioxidants (Basel). 2023 Jun 14;12(6):1270. doi: 10.3390/antiox12061270. Antioxidants (Basel). 2023. PMID: 37372000 Free PMC article.
• Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells.
  Lee JH, Subedi L, Kim SY. Lee JH, et al. Cells. 2020 Jan 17;9(1):234. doi: 10.3390/cells9010234. Cells. 2020. PMID: 31963523 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • S. Karger AG, Basel, Switzerland

• Other Literature Sources

  • scite Smart Citations