| First Author | Singaravelu K | Year | 2011 |
| Journal | Am J Physiol Renal Physiol | Volume | 300 |
| Issue | 5 | Pages | F1130-41 |
| PubMed ID | 21307125 | Mgi Jnum | J:171466 |
| Mgi Id | MGI:4949988 | Doi | 10.1152/ajprenal.00591.2010 |
| Citation | Singaravelu K, et al. (2011) p53 target Siva regulates apoptosis in ischemic kidneys. Am J Physiol Renal Physiol 300(5):F1130-41 |
| abstractText | The role of p53 in inducing apoptosis following acute kidney injury is well-established; however, the molecular mechanisms remain largely unknown. We report here that the p53 proapoptotic target Siva and its receptor CD27, a member of the tumor necrosis factor receptor family, are upregulated following renal ischemia-reperfusion injury (IRI). Inhibition of Siva using antisense oligonucleotides conferred functional and morphological protection, and it prevented apoptosis postrenal IRI in mice. Renal IRI in CD27-deficient mice displayed functional protection and partial inhibition of apoptosis, suggesting an incomplete role for CD27 in Siva-mediated apoptosis. To further elucidate mechanisms by which Siva elicits apoptosis, in vitro studies were performed. In Siva-transfected LLC-PK(1 )cells, Siva is persistently expressed in the nucleus at 3 h onwards and its translocation to mitochondria and the plasma membrane occurred at 6 h. Moreover, Siva overexpression induced mitochondrial permeability, cytochrome c release, caspase-8 and -9 activation, translocation of apoptosis-inducing factor (AIF) to the nucleus, and apoptosis. Inhibition of Siva in ischemic kidneys prevented mitochondrial release of cytochrome c and AIF. These data indicate that Siva function is pivotal in regulating apoptosis in the pathology of renal IRI. Targeting Siva may offer a potential therapeutic strategy for renal IRI. |
