Genetic disruption of Abl nuclear import reduces renal apoptosis in a mouse model of cisplatin-induced nephrotoxicity.

ABSTRACT: DNA damage activates nuclear Abl tyrosine kinase to stimulate intrinsic apoptosis in cancer cell lines and mouse embryonic stem cells. To examine the in vivo function of nuclear Abl in apoptosis, we generated Abl-μNLS (μ, mutated in nuclear localization signals) mice. We show here that cisplatin-induced apoptosis is defective in the renal proximal tubule cells (RPTC) from the Abl(μ/μ) mice. When injected with cisplatin, we found similar levels of platinum in the Abl(+/+) and the Abl(μ/μ) kidneys, as well as similar initial inductions of p53 and PUMAα expression. However, the accumulation of p53 and PUMAα could not be sustained in the Abl(μ/μ) kidneys, leading to reductions in renal apoptosis and tubule damage. Co-treatment of cisplatin with the Abl kinase inhibitor, imatinib, reduced the a

SUBMITTER: Sridevi P 

PROVIDER: S-EPMC3679464 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature