@article{PrueferSchuchardtToelleetal.2014, author = {Pruefer, Jasmin and Schuchardt, Mirjam and Toelle, Markus and Pruefer, Nicole and Hoehne, Matthias and Zidek, Walter and van der Giet, Markus}, title = {Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: Induction of mineralization}, series = {PLoS one}, volume = {9}, journal = {PLoS one}, number = {7}, publisher = {PLoS}, address = {San Fransisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0101709}, pages = {8}, year = {2014}, abstract = {Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteochondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.}, language = {en} } @article{SulpicePylIshiharaetal.2009, author = {Sulpice, Ronan and Pyl, Eva-Theresa and Ishihara, Hirofumi and Trenkamp, Sandra and Steinfath, Matthias and Witucka-Wall, Hanna and Gibon, Yves and Usadel, Bj{\"o}rn and Poree, Fabien and Piques, Maria Conceicao and von Korff, Maria and Steinhauser, Marie Caroline and Keurentjes, Joost J. B. and Guenther, Manuela and Hoehne, Melanie and Selbig, Joachim and Fernie, Alisdair R. and Altmann, Thomas and Stitt, Mark}, title = {Starch as a major integrator in the regulation of plant growth}, issn = {0027-8424}, doi = {10.1073/pnas.0903478106}, year = {2009}, abstract = {Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94 Arabidopsis accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1- phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production.}, language = {en} }