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PhD SP11

Sequestering of reactive carbonyl species (RCS) by carnosine ameliorates vascular damage in vitro and vivo

Supervisor (Mannheim): Benito Yard
Co-Supervisor (Groningen): Jacob van den Born
Graduate: Xinmiao Zhang

Project description

In this project we will investigate three major questions: (i) does chronic exposure of endothelial cells and renal proximal tubular epithelial cells (PTEC) to lipid and sugar derived reactive carbonyl species (RCS), e.g. acrolein ( ACRO) or MGO, deplete GSH and does this lead to marked changes in gene expression? (ii) Are changes in gene expression sustained by histone modification and/or induction of miR? (iii) Does carnosine ameliorate these changes in cell culture models. Are carnosine-RCS adducts found in vivo in carnosine treated T2D BTBRob/ob mice, are they discarded via the urine or accumulating in the kidney. Does this change in BTBRob/ob mice over-expressing the human serum carnosinase (CNDP1) gene.


  1.  O'Toole TE. Et al,  Toxicol Sci. 2014 Aug 1;140(2):271-82
  2. DeJarnett N. et al, J Am Heart Assoc. 2014 Aug 6;3(4).
  3. Schophuizen CM. et al, Pflugers Arch. 2013 Dec;465(12):1701-14
  4. *Zhang S. et al, J Diabetes Res. 2016;2016:8710432.
  5. *Riedl E. et al, Cell Physiol Biochem. 2011;28(2):279-88.
  6. *Riedl E. et al Diabetes. 2010;59(8):1984-90
  7. Regazzoni L. et al, Sci Rep. 2016;6:27224.
  8. *Stamellou E. et al, PLoS One. 2014 Jun 13;9(6):e99298
  9. *Everaert I. et al, Am J Physiol Renal Physiol. 2012 Jun 15;302(12):F1537-44.

* Own publications

Methods that will be used

Cell Culture (human umbilical vein endothelial cells, PTEC) Mouse models (BTBRob/ob), gene-expression profiling Affymetrix/RNAseq, qPCR, Westernblotting, reporter assays

Collaboration Partners

  • Jacob van den Born, Groningen
  • Peter Nawroth, Heidelberg
  • Jens Kroll, Mannheim
  • Jonathan Sleeman, Mannheim