Endoplasmic reticulum stress-mediated activation of p38 MAPK, Caspase-2 and Caspase-8 leads to abrin-induced apoptosis.

Bibliographic Details
Title: Endoplasmic reticulum stress-mediated activation of p38 MAPK, Caspase-2 and Caspase-8 leads to abrin-induced apoptosis.
Authors: Ritu Mishra, Anjali A Karande
Source: PLoS ONE, Vol 9, Iss 3, p e92586 (2014)
Publisher Information: Public Library of Science (PLoS), 2014.
Publication Year: 2014
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: Abrin from Abrus precatorius plant is a potent protein synthesis inhibitor and induces apoptosis in cells. However, the relationship between inhibition of protein synthesis and apoptosis is not well understood. Inhibition of protein synthesis by abrin can lead to accumulation of unfolded protein in the endoplasmic reticulum causing ER stress. The observation of phosphorylation of eukaryotic initiation factor 2α and upregulation of CHOP (CAAT/enhancer binding protein (C/EBP) homologous protein), important players involved in ER stress signaling by abrin, suggested activation of ER stress in the cells. ER stress is also known to induce apoptosis via stress kinases such as p38 MAPK and JNK. Activation of both the pathways was observed upon abrin treatment and found to be upstream of the activation of caspases. Moreover, abrin-induced apoptosis was found to be dependent on p38 MAPK but not JNK. We also observed that abrin induced the activation of caspase-2 and caspase-8 and triggered Bid cleavage leading to mitochondrial membrane potential loss and thus connecting the signaling events from ER stress to mitochondrial death machinery.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: http://europepmc.org/articles/PMC3963924?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0092586
Access URL: https://doaj.org/article/4c0f663b03b94fdb88315de92b5c9e31
Accession Number: edsdoj.4c0f663b03b94fdb88315de92b5c9e31
Database: Directory of Open Access Journals
More Details
ISSN:19326203
DOI:10.1371/journal.pone.0092586
Published in:PLoS ONE
Language:English