Related Experiment Video

Updated: Dec 25, 2025

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

2.5K

The PERK/eIF2α/ATF4/CHOP pathway plays a role in regulating monocrotaline-induced endoplasmic reticulum stress in rat

Yazhou Guo1, Rong Guo1, Yongxia Su1

  • 1College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China; Institute of Poisonous Plants in Western China, Northwest A&F University, Yangling, Shaanxi 712100, China.

Research in Veterinary Science
|April 1, 2020
PubMed

Insights

Monocrotaline (MCT) induces liver damage by causing endoplasmic reticulum (ER) stress in rats. This study reveals that MCT activates key ER stress pathways, contributing to hepatotoxicity.

Area of Science:

  • Toxicology
  • Cellular Biology
  • Biochemistry

Background:

  • Monocrotaline (MCT), a pyrrolizidine alkaloid, is known for its hepatotoxicity.
  • Apoptosis is a key mechanism in MCT-induced liver injury.
  • The precise role of endoplasmic reticulum (ER) stress in MCT hepatotoxicity remains unclear.

Purpose of the Study:

  • To investigate the role of ER stress in Monocrotaline-induced hepatotoxicity in a rat model.
  • To elucidate the specific ER stress pathways involved in MCT-induced liver damage.

Main Methods:

  • Adult male rats were divided into three groups: control, low-dose MCT, and high-dose MCT.
  • Liver tissues were collected 48 hours post-administration.
  • Western blotting was used to analyze the expression of ER stress-related proteins.

Main Results:

  • MCT administration led to a dose-dependent increase in ER stress markers: GRP78, p-IRE1α, ATF6, and caspase-12.
  • Key proteins in the PERK/eIF2α/ATF4/CHOP pathway, including p-PERK, p-eIF2α, ATF4, and CHOP, were significantly upregulated by MCT.
  • These findings indicate MCT induces ER stress in rat liver.

Conclusions:

  • Monocrotaline induces significant endoplasmic reticulum stress in the rat liver.
  • The PERK/eIF2α/ATF4/CHOP pathway plays a crucial role in mediating MCT-induced ER stress and subsequent hepatotoxicity.
Keywords:
Endoplasmic reticulum stressHepatotoxicityMonocrotalinePERK-eIF2a-ATF4-CHOP pathway

More Related Videos

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen09:44

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

Published on: November 27, 2019

10.8K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.7K

Related Concept Videos

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...
6.1K
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...
2.9K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
6.7K
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...
5.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.7K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
18.2K