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Updated: Jun 15, 2026
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
The apoptotic effect of oral administration of microcystin-RR on mice liver
Pu Huang1, Qun Zheng, Li-Hong Xu
1Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Abstract:
Microcystin produced by cyanobacteria in diverse water systems is a potent hepatotoxin that has been documented to induce hepatocyte apoptosis and liver injury. There are more than eighty reported microcystins. The present work aimed at investigating the apoptotic effect of MC-RR (a common member of microcystin family), and its related mechanism. MC-RR was administered orally to ICR mice for 7 days with different dosages. Apoptotic cell death in liver was detected by TUNEL assay, and the expression levels of Bcl-2, Bax and p53, GRP 78 and CHOP which have been reported to be related to apoptosis and ER stress were determined via western-blot. The activity of PP2A was measured using the serine-threonine phosphatase assay system and PP2A A subunit expression at both transcription and protein levels was measured by RT-PCR and western blot, respectively. A significant difference was observed on the number of TUNEL positive liver cells between the control and MC-RR-treated groups. The expression levels of Bcl-2, Bax, p53, and GRP 78 in MC-RR-treated groups were altered significantly compared to the control, but no obvious alteration was found in CHOP expression. The PP2A activity and A subunit expression did not manifest any obvious change at both transcription and protein levels. The results indicated that oral exposure to MC-RR can cause apoptosis as well as moderate ER stress in mice liver. The mitochondrial pathway via Bcl-2 family members may contribute to the apoptosis. However, PP2A may not be involved in the regulation of apoptotic process under the current conditions.
Insights
Oral exposure to microcystin-RR (MC-RR) induces liver apoptosis and moderate endoplasmic reticulum stress in mice. The mitochondrial pathway, involving Bcl-2 family proteins, contributes to apoptosis, while protein phosphatase 2A (PP2A) appears uninvolved.
Area of Science:
- Toxicology
- Cell Biology
- Environmental Health
Background:
- Microcystins (MCs) are cyanobacterial hepatotoxins causing liver injury.
- MC-RR is a common microcystin variant with documented toxic effects.
- Understanding MC-RR's apoptotic mechanisms is crucial for risk assessment.
Purpose of the Study:
- To investigate the apoptotic effects of oral MC-RR exposure in mice.
- To elucidate the molecular mechanisms underlying MC-RR-induced liver apoptosis and ER stress.
- To assess the involvement of the mitochondrial pathway and PP2A in MC-RR toxicity.
Main Methods:
- Oral administration of MC-RR to ICR mice for 7 days.
- TUNEL assay for detecting apoptotic cells in liver tissue.
- Western blot analysis for Bcl-2, Bax, p53, GRP78, and CHOP expression.
- RT-PCR and Western blot for PP2A A subunit expression.
- Serine-threonine phosphatase assay for PP2A activity measurement.
Main Results:
- Significant increase in TUNEL-positive cells in MC-RR treated mice.
- Altered expression of Bcl-2, Bax, p53, and GRP78, indicating mitochondrial pathway involvement and ER stress.
- No significant changes in CHOP expression.
- No significant alterations in PP2A activity or A subunit expression.
Conclusions:
- Oral MC-RR exposure induces liver apoptosis and moderate ER stress in mice.
- The mitochondrial pathway, mediated by Bcl-2 family proteins, plays a role in MC-RR-induced apoptosis.
- PP2A is likely not involved in the regulation of MC-RR-induced apoptosis under these experimental conditions.
