Related Experiment Video

Updated: Jun 26, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

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

Kurinji Singaravelu1, Kishor Devalaraja-Narashimha, Brynn Lastovica

  • 1Dept. of Cellular and Integrative Physiology, Nebraska Medical Center, Omaha, NE 68198-5850, USA.

American Journal of Physiology. Renal Physiology
|January 23, 2009
PubMed

Insights

The p53 apoptosis effector PERP is crucial in kidney injury. This study shows PERP triggers cell death in renal ischemia-reperfusion injury, offering a potential therapeutic target.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Death Research

Background:

  • The p53 tumor suppressor gene is vital for apoptosis during renal ischemia-reperfusion injury (IRI).
  • The p53 apoptosis effector related to PMP-22 (PERP) is a p53 transcriptional target involved in apoptosis.
  • Understanding PERP's role in renal IRI is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of PERP in the p53-dependent apoptotic pathway in renal IRI.
  • To determine if PERP mediates apoptosis in proximal tubular cells (PTC) during hypoxic injury.
  • To evaluate PERP as a potential therapeutic target for renal IRI.

Main Methods:

  • Analyzing PERP mRNA and protein expression in ischemic kidney tissues post-reperfusion.
  • Overexpressing PERP in PTC to assess its effect on apoptosis following hypoxia.
  • Utilizing short hairpin RNA (shRNA) to silence PERP and evaluate its impact on hypoxia-mediated injury.
  • Measuring mitochondrial permeability, cytochrome c and apoptosis-inducing factor (AIF) release, and caspase 9 activation.

Main Results:

  • PERP mRNA and protein levels were significantly induced in outer medullary PTC of ischemic kidneys in a p53-dependent manner.
  • PERP overexpression in PTC enhanced hypoxia-induced apoptosis by increasing mitochondrial permeability and releasing cytochrome c and AIF.
  • PERP silencing via shRNA protected PTC from hypoxia-induced apoptosis by preventing mitochondrial dysfunction and subsequent factor translocation.
  • Caspase 9 activation was observed following PERP overexpression.

Conclusions:

  • PERP acts as a key effector in p53-mediated apoptotic pathways during renal IRI.
  • PERP contributes to renal cell death by inducing mitochondrial dysfunction and apoptosis.
  • PERP represents a promising therapeutic target for mitigating renal IRI.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...