Biomedical subjects

Kay-Dietrich Wagner

Publications and source records attributed to Kay-Dietrich Wagner.

21 records · Page 2Linked to original sources

PubMed2002

Decreased susceptibility of cardiac function to hypoxia-reoxygenation in renin-angiotensinogen transgenic rats.

We tested the hypothesis that the renin-angiotensin system (RAS) protects the contractile function of the myocardium against the damaging effect of hypoxia-reoxygenation. For this purpose, the contractility of isolated papillary muscles from wild-type (WT) rats and from rats expressing human renin and angiotensinogen as transgenes (TGR) was compared. After 15 min of hypoxia, peak force (PF) was decreased to 24 +/- 5% of the normoxic values in TGR (n = 10) and to 18 +/- 1% in WT rats (n = 12). PF and relaxation rates recovered completely in TGR but not in WT rats during 45 min of reoxygenation. Improved contractility of the papillary muscles from TGR during hypoxia-reoxygenation correlated with increased glutathione peroxidase activities and creatine kinase (CK)-MB and CK-BB isoenzyme levels. On the other hand, inhibition of the RAS with ramipril (1 mg/kg body wt for 3 wk) in WT animals resulted in deterioration of the contractile function of the papillary muscles during reoxygenation compared with untreated rats. These findings suggest that activation of the RAS protects contractile function of the cardiac muscle against hypoxia-reoxygenation, possibly through changes in CK isoenzymes and enhanced antioxidant capacity.

Animals↗

PubMed2002

The Wilms' tumor suppressor Wt1 is associated with the differentiation of retinoblastoma cells.

We have demonstrated recently that Wilms' tumor suppressor 1 (Wt1),in addition to its role in genitourinary formation,is required for the differentiation of ganglion cells in the developing retina. Here we provide further evidence that Wt1 is associated with neuronal differentiation. Thus, the retinoblastoma-derived human cell line, Y-79, contained robust amounts of Wt1 mRNA and protein. Wt1 expression was down-regulated upon laminin-induced differentiation of Y-79 into neuron-like cells. Inhibition of Wt1 with antisense oligonucleotides dramatically reduced the capacity of undifferentiated Y-79 cells to undergo neuronal differentiation, whereas sense and missense oligonucleotides had no effect. Wt1 immunoreactivity was also detected in solid retinoblastomas, in which it resided mainly in areas with moderate proliferative activity. These findings suggest a role for Wt1 in the differentiation of retinoblastoma cells. Furthermore, Wt1 expression in retinoblastoma may reflect the potential of these tumors to initiate the early steps of neuronal differentiation.

Cell Differentiation↗

PubMed2001

Activation of vitamin D receptor by the Wilms' tumor gene product mediates apoptosis of renal cells.

The Wilms' tumor transcription factor WT1 is required for kidney development, but little is known about WT1 downstream signaling in renal cells. This study reported an approximately fivefold upregulation of vitamin D receptor (VDR) mRNA and protein in human embryonic kidney (HEK) 293 cells that stably expressed WT1 at a level comparable to the developing kidney in vivo. Co-transfection of HEK 293 cells with expression plasmids encoding four different WT1 splicing variants stimulated mouse vdr promoter activity more than fourfold. A 201-bp fragment was identified in the proximal vdr promoter that was required for transactivation by WT1. This critical sequence contained a predicted WT1 consensus site, which bound to recombinant WT1 protein. Temporal changes of vdr and wt1 mRNA levels in developing rat kidneys were correlated closely. The active metabolite 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) strongly inhibited the proliferation of wt1-transfected HEK 293 cells. Exposure to 1,25-(OH)(2)D(3) caused apoptosis of cultured wt1 immunopositive cells from mouse embryonic kidney cortex. These findings suggest that transcriptional activation of the VDR by WT1 can mediate programmed death of renal embryonic cells in response to 1,25-(OH)(2)D(3). The results provide the first evidence for a role of the vitamin D endocrine system in renal cell growth and differentiation during development.

Animals↗