Related Experiment Video

Updated: Feb 14, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

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

961

Diepoxybutane-induced apoptosis is mediated through the ERK1/2 pathway

E Eluka-Okoludoh1,2, A J Ewunkem2, S Thorpe1

  • 11 Department of Biology, North Carolina A&T State University, Greensboro, NC, USA.

Human & Experimental Toxicology
|February 7, 2018
PubMed

Insights

Diepoxybutane (DEB), a butadiene metabolite, triggers apoptosis in human cells via the MEK-ERK1/2-p53 pathway. Inhibiting this pathway reduces DEB-induced cell death, offering insights into its toxicity.

Area of Science:

  • Toxicology
  • Cell Biology
  • Molecular Biology

Background:

  • Diepoxybutane (DEB) is a potent metabolite of butadiene, a regulated air pollutant.
  • Previous research established DEB-induced, p53-dependent, mitochondrial-mediated apoptosis in human lymphoblasts.

Purpose of the Study:

  • To investigate the role of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway in DEB-induced apoptotic signaling.
  • To elucidate the specific signaling cascade involved in DEB toxicity.

Main Methods:

  • Human lymphoblasts were exposed to DEB.
  • Levels of activated ERK1/2 and mitogen-activated protein (MAP) kinase/ERK1/2 kinase (MEK) were measured.
  • The MEK inhibitor PD98059 and ERK1/2 siRNA were used to block the pathway.
  • Apoptosis, ERK1/2 activation, and p53/phospho-p53 levels were assessed.

Main Results:

  • DEB exposure significantly upregulated ERK1/2 and MEK levels in human lymphoblasts.
  • Inhibition of MEK or ERK1/2 significantly reduced DEB-induced apoptosis.
  • Blocking the MEK-ERK1/2 pathway also decreased p53 and phospho-p53 levels.

Conclusions:

  • DEB induces apoptosis in human lymphoblasts through the MEK-ERK1/2-p53 signaling pathway.
  • This study is the first to implicate ERK1/2 pathway activation in mediating DEB-induced apoptosis.
  • Findings enhance understanding of DEB toxicity mechanisms and apoptotic signaling in human lymphoblasts.
Keywords:
DiepoxybutaneERK1/2apoptosisbutadieneextracellular signal–regulated protein kinasep53

More Related Videos

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 308:20

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Published on: December 20, 2013

20.7K
Finger-stick Blood Sampling Methodology for the Determination of Exercise-induced Lymphocyte Apoptosis04:37

Finger-stick Blood Sampling Methodology for the Determination of Exercise-induced Lymphocyte Apoptosis

Published on: February 24, 2011

12.5K

Related Concept Videos

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...
15.3K
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
49.4K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
11.9K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
111.6K
Other Glycolytic Pathways01:24

Other Glycolytic Pathways

The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
1.0K
Respiration Pathways01:26

Respiration Pathways

Cellular respiration is a fundamental metabolic process that enables organisms to generate energy from organic molecules. One of its central pathways is the tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, which plays a crucial role in energy production and biosynthetic processes.Conversion of Pyruvate to Acetyl-CoAThe pyruvate generated from glycolysis undergoes oxidative decarboxylation by the pyruvate dehydrogenase complex, producing acetyl-CoA, one molecule of NADH, and one...
798