calpain and Polycystic-Kidney--Autosomal-Dominant

calpain has been researched along with Polycystic-Kidney--Autosomal-Dominant* in 1 studies

Other Studies

1 other study(ies) available for calpain and Polycystic-Kidney--Autosomal-Dominant

Article	Year
Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proceedings of the National Academy of Sciences of the United States of America, 2005, May-10, Volume: 102, Issue:19 We have previously demonstrated an increase in proapoptotic caspase-3 in the kidney of Han:SPRD rats with polycystic kidney disease (PKD). The aim of the present study was to determine the effect of caspase inhibition on tubular cell apoptosis and proliferation, cyst formation, and renal failure in the Han:SPRD rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+) male rats were weaned at 3 weeks of age and then treated with the caspase inhibitor IDN-8050 (10 mg/kg per day) by means of an Alzet (Palo Alto, CA) minipump or vehicle [polyethylene glycol (PEG 300)] for 5 weeks. The two-kidney/total body weight ratio more than doubled in Cy/+ rats compared with +/+ rats. IDN-8050 significantly reduced the kidney enlargement by 44% and the cyst volume density by 29% in Cy/+ rats. Cy/+ rats with PKD have kidney failure as indicated by a significant increase in blood urea nitrogen. IDN-8050 significantly reduced the increase in blood urea nitrogen in the Cy/+ rats. The number of proliferating cell nuclear antigen-positive tubular cells and apoptotic tubular cells in non-cystic and cystic tubules was significantly reduced in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. On immunoblot, the active form of caspase-3 (20 kDa) was significantly decreased in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. In summary, in a rat model of PKD, caspase inhibition with IDN-8050 (i) decreases apoptosis and proliferation in cystic and noncystic tubules; (ii) inhibits renal enlargement and cystogenesis, and (iii) attenuates the loss of kidney function. Topics: Animals; Animals, Genetically Modified; Apoptosis; Blood Urea Nitrogen; Calpain; Caspase 3; Caspase Inhibitors; Caspases; Cathepsin B; Cell Proliferation; Disease Progression; Enzyme Inhibitors; Heterozygote; Immunoblotting; In Situ Nick-End Labeling; Inhibitory Concentration 50; Kidney; Male; Mice; Mice, Transgenic; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Proliferating Cell Nuclear Antigen; Rats	2005

Article

Year

Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease.

Proceedings of the National Academy of Sciences of the United States of America, 2005, May-10, Volume: 102, Issue:19

We have previously demonstrated an increase in proapoptotic caspase-3 in the kidney of Han:SPRD rats with polycystic kidney disease (PKD). The aim of the present study was to determine the effect of caspase inhibition on tubular cell apoptosis and proliferation, cyst formation, and renal failure in the Han:SPRD rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+) male rats were weaned at 3 weeks of age and then treated with the caspase inhibitor IDN-8050 (10 mg/kg per day) by means of an Alzet (Palo Alto, CA) minipump or vehicle [polyethylene glycol (PEG 300)] for 5 weeks. The two-kidney/total body weight ratio more than doubled in Cy/+ rats compared with +/+ rats. IDN-8050 significantly reduced the kidney enlargement by 44% and the cyst volume density by 29% in Cy/+ rats. Cy/+ rats with PKD have kidney failure as indicated by a significant increase in blood urea nitrogen. IDN-8050 significantly reduced the increase in blood urea nitrogen in the Cy/+ rats. The number of proliferating cell nuclear antigen-positive tubular cells and apoptotic tubular cells in non-cystic and cystic tubules was significantly reduced in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. On immunoblot, the active form of caspase-3 (20 kDa) was significantly decreased in IDN-8050-treated Cy/+ rats compared with vehicle-treated Cy/+ rats. In summary, in a rat model of PKD, caspase inhibition with IDN-8050 (i) decreases apoptosis and proliferation in cystic and noncystic tubules; (ii) inhibits renal enlargement and cystogenesis, and (iii) attenuates the loss of kidney function.

Topics: Animals; Animals, Genetically Modified; Apoptosis; Blood Urea Nitrogen; Calpain; Caspase 3; Caspase Inhibitors; Caspases; Cathepsin B; Cell Proliferation; Disease Progression; Enzyme Inhibitors; Heterozygote; Immunoblotting; In Situ Nick-End Labeling; Inhibitory Concentration 50; Kidney; Male; Mice; Mice, Transgenic; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Proliferating Cell Nuclear Antigen; Rats

2005