Related Experiment Video

Updated: Oct 2, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Calpain activation after mitochondrial permeability transition in microcystin-induced cell death in rat hepatocytes

Wen-Xing Ding1, Han-Ming Shen, Choon-Nam Ong

  • 1Center for Environmental and Occupational Health, Department of Community, Occupational, and Family Medicine, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore.

Biochemical and Biophysical Research Communications
|February 16, 2002
PubMed

Insights

Microcystin-LR (MLR) triggers mitochondrial permeability transition (MPT) and apoptosis in liver cells. This study reveals calpain activation, not caspases, mediates MLR-induced cell death, offering new therapeutic targets.

Area of Science:

  • Hepatology
  • Toxicology
  • Cell Biology

Background:

  • Microcystin-LR (MLR) is a hepatotoxin known to induce mitochondrial permeability transition (MPT) and apoptosis.
  • The precise downstream signaling pathways following MPT in MLR-treated hepatocytes require further elucidation.

Purpose of the Study:

  • To investigate the molecular events downstream of MPT in MLR-induced hepatocyte apoptosis.
  • To determine the role of caspases and calpains in MLR-induced cell death.

Main Methods:

  • Primary rat hepatocyte culture.
  • Treatment with MLR, mitochondrial electron transport chain (ETC) inhibitors, cyclosporin A (CsA), and calpain inhibitors (ALLN, ALLM).
  • Assessment of MPT onset, cytochrome c release, caspase activation (caspase-9, -3), and calpain activation.

Main Results:

  • MLR-induced MPT was prevented by ETC inhibitors, implicating the mitochondrial ETC.
  • MLR caused cytochrome c release, which was inhibited by CsA and ETC inhibitors.
  • Cytochrome c release did not activate caspases -9 and -3.
  • MLR activated calpain, likely via mitochondrially released Ca(2+).
  • Calpain inhibitors (ALLN, ALLM) and CsA blocked MLR-induced calpain activation and cell death.

Conclusions:

  • Calpain activation, rather than caspase activation, is a critical mediator of MLR-induced apoptosis in rat hepatocytes.
  • MLR-induced cell death involves a post-mitochondrial event pathway centered on calpain.
  • Targeting calpain may offer a novel therapeutic strategy against MLR toxicity.

More Related Videos

Mitochondrial Ca2+ Retention Capacity Assay and Ca2+-triggered Mitochondrial Swelling Assay05:53

Mitochondrial Ca2+ Retention Capacity Assay and Ca2+-triggered Mitochondrial Swelling Assay

Published on: May 1, 2018

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

Related Concept Videos

Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...
Cellular Injury I: Introduction01:00

Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...