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