Induction of proapoptotic Daxx following ischemic acute kidney injury.
Transcriptome profiling has shown that the pro-apoptotic death-domain-associated protein Daxx is rapidly induced in the kidney of animals following ischemic injury. Here we found that Daxx protein was increased 5-fold in tubule cells in both animal and human models of ischemic acute kidney injury. Further there was upregulation of its primary interacting partner, Fas and phosphorylation of its primary downstream activator (JNK) in parallel to Daxx induction. In cultured tubule cells, partial ATP depletion resulted in a rapid induction of Daxx, Fas, JNK phosphorylation and apoptosis. Antisense oligonucleotides to Daxx and specific JNK inhibitors blunted the apoptotic response to ATP depletion. These studies indicate that Daxx may play an unrecognized role in the early apoptotic response to ischemic renal injury.
Ma
Qing
Q
Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Devarajan
Prasad
P
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000172:deficiency; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007511:Ischemia; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics*; D010766:Phosphorylation; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C491473:Daxx protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019014:fas Receptor; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases