PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia

Kurinji Singaravelu, Kishor Devalaraja-Narashimha, Brynn Lastovica, Babu J Padanilam

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The p53 tumor suppressor gene plays a crucial role in mediating apoptotic cell death in renal ischemia-reperfusion injury (IRI). To further elucidate the p53-dependent pathway, we investigated the role of the p53 apoptosis effector related to PMP-22 (PERP), an apoptosisassociated p53 transcriptional target. PERP mRNA and protein are highly induced in the outer medullary proximal tubular cells (PTC) of ischemic kidneys postreperfusion at 3, 12, and 24 h in a p53-dependent manner. In PTC, overexpression of PERP augmented the rate of apoptosis following hypoxia by inducing mitochondrial permeability and subsequent release of cytochrome c, apoptosis-inducing factor (AIF), and caspase 9 activation. In addition, silencing of the PERP gene with short hairpin RNA prevented apoptosis in hypoxia-mediated injury by precluding mitochondrial dysfunction and consequent cytochrome c and AIF translocation. These data suggest that PERP is a key effector of p53-mediated apoptotic pathways and is a potential therapeutic target for renal IRI.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 1 2009

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Cell Death
Ischemia
Apoptosis
Kidney
Apoptosis Inducing Factor
Cytochromes c
Reperfusion Injury
Caspase 9
Tumor Suppressor Genes
Small Interfering RNA
Permeability
Messenger RNA
Wounds and Injuries
Genes
Proteins
Hypoxia

Keywords

  • AIF
  • Acute renal failure
  • Caspase
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia. / Singaravelu, Kurinji; Devalaraja-Narashimha, Kishor; Lastovica, Brynn; Padanilam, Babu J.

In: American Journal of Physiology - Renal Physiology, Vol. 296, No. 4, 01.04.2009.

Research output: Contribution to journalArticle

Singaravelu, Kurinji ; Devalaraja-Narashimha, Kishor ; Lastovica, Brynn ; Padanilam, Babu J. / PERP, a p53 proapoptotic target, mediates apoptotic cell death in renal ischemia. In: American Journal of Physiology - Renal Physiology. 2009 ; Vol. 296, No. 4.
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