Related Experiment Video

Updated: Aug 19, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

ERK1/2-dependent regulation of U937 cell survival after exposure to peroxynitrite

Ilaria Tommasini1, Liana Cerioni, Andrea Guidarelli

  • 1Istituto di Farmacologia e Farmacognosia, Università degli Studi di Urbino "Carlo Bo," Via S. Chiara, 27-61029 Urbino (PU), Italy.

Biochemical and Biophysical Research Communications
|March 16, 2005
PubMed

Insights

Short-term serum-free growth primes U937 cells for peroxynitrite-induced necrosis via mitochondrial permeability transition (MPT). This occurs due to inhibited extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, limiting survival signaling.

Area of Science:

  • Cellular Biology
  • Biochemistry
  • Toxicology

Background:

  • U937 cells grown in serum-free medium exhibit heightened sensitivity to peroxynitrite.
  • Peroxynitrite can induce cell death through mitochondrial permeability transition (MPT).

Purpose of the Study:

  • To investigate the mechanism by which serum-free conditions sensitize U937 cells to peroxynitrite-induced necrosis.
  • To elucidate the role of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and arachidonic acid (AA) release in this process.

Main Methods:

  • U937 cell culture under serum-free and serum-containing conditions.
  • Exposure to peroxynitrite and assessment of cell viability.
  • Measurement of ERK1/2 phosphorylation and arachidonic acid (AA) release.

Main Results:

  • Serum-free growth potentiated peroxynitrite-induced necrosis, dependent on mitochondrial permeability transition (MPT).
  • Peroxynitrite inhibited ERK1/2 phosphorylation, which is crucial for AA release.
  • Reduced AA availability impaired survival signaling, leading to MPT-based necrosis.

Conclusions:

  • Basal ERK1/2 phosphorylation is critical for U937 cell survival against peroxynitrite.
  • Inhibition of ERK1/2 phosphorylation and subsequent AA release mediates peroxynitrite-induced necrosis in serum-deprived cells.

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

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
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...