Apoptosis in polycystic kidney disease: involvement of caspases

Shujath M. Ali, Victoria Y. Wong, Kristine Kikly, Todd A. Fredrickson, Paul M. Keller, Walter E. DeWolf, Dennis Lee, David P. Brooks
2000 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
Brooks. Apoptosis in polycystic kidney disease: involvement of caspases. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278: R763-R769, 2000.-Polycystic kidney disease (PKD) is characterized by the development of large renal cysts and progressive loss of renal function. Although the cause of the development of renal cysts is unknown, recent evidence suggests that excessive apoptosis occurs in PKD. With the use of terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, we
more » ... ling staining, we have confirmed the presence of apoptotic bodies in cystic kidneys of congenital polycystic kidney (cpk) disease mice carrying a homozygous mutation at 3 wk of age. Apoptosis was localized primarily to the interstitium with little evidence of cell death in cyst epithelium or noncystic tubules. In addition, we observed that the expression of various caspases, bax and bcl-2, was upregulated in cystic kidneys. With the use of various substrates in enzyme activity assays, we have demonstrated a greater than sevenfold increase in caspase 4 activity and a sixfold increase in caspase 3 activity. These data suggest that there is a caspasedependent apoptosis pathway associated with PKD and support the hypothesis that apoptotic cell death contributes to cyst formation in PKD.
doi:10.1152/ajpregu.2000.278.3.r763 pmid:10712299 fatcat:befd6yvt7vdb7jwhehgk24v5gm