Related Experiment Video

Updated: Oct 5, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

The von Hippel-Lindau gene product inhibits renal cell apoptosis via Bcl-2-dependent pathways

P Devarajan1, M De Leon, F Talasazan

  • 1Department of Pediatrics, Division of Pediatric Nephrology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. pdevaraj@aecom.yu.edu

The Journal of Biological Chemistry
|August 22, 2001
PubMed

Insights

The von Hippel-Lindau (VHL) gene product protects kidney cells from apoptosis during chemical hypoxia. This protection is mediated by the Bcl-2 protein, highlighting a novel therapeutic target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The von Hippel-Lindau (VHL) gene is known to have a protective role against apoptosis.
  • The precise mechanisms underlying VHL's anti-apoptotic function remain largely unelucidated.
  • Renal cells are susceptible to apoptosis under conditions of chemical hypoxia.

Purpose of the Study:

  • To investigate the role of VHL in renal cell apoptosis induced by chemical hypoxia.
  • To elucidate the molecular pathways involved in VHL-mediated protection against apoptosis.

Main Methods:

  • Utilized four VHL-negative and two VHL-positive renal carcinoma cell lines.
  • Subjected cells to chemical hypoxia (glucose deprivation and antimycin).
  • Assessed apoptosis through morphological changes and DNA fragmentation; analyzed caspase activation, cytochrome c release, and Bcl-2 expression.

Main Results:

  • VHL-negative cells underwent apoptosis with significant caspase 9 activation and cytochrome c release upon chemical hypoxia.
  • Reintroduction of VHL expression or Bcl-2 overexpression conferred resistance to apoptosis.
  • VHL-positive cells exhibited minimal caspase activation and cytochrome c release, alongside a 5-fold increase in Bcl-2 expression.

Conclusions:

  • VHL protects renal cells from apoptosis during chemical hypoxia.
  • This protective effect is mediated through Bcl-2-dependent pathways.
  • VHL's role in regulating Bcl-2 offers potential therapeutic strategies for renal cell carcinoma.

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 Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
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...