PUBLICATION
Inhibition of endoplasmic reticulum stress-related autophagy attenuates MCLR-induced apoptosis in zebrafish testis and mouse TM4 cells
- Authors
- Wu, Z., Wang, F., Hu, L., Zhang, J., Chen, D., Zhao, S.
- ID
- ZDB-PUB-210629-26
- Date
- 2021
- Source
- Ecotoxicology and environmental safety 221: 112438 (Journal)
- Registered Authors
- Keywords
- Apoptosis, Autophagy, Endoplasmic reticulum stress, MCLR, Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects*
- Autophagosomes/metabolism
- Autophagosomes/ultrastructure
- Autophagy/drug effects*
- Cell Line
- Endoplasmic Reticulum Stress/drug effects*
- Male
- Mice
- Microcystins/toxicity*
- Phenylbutyrates/pharmacology
- Signal Transduction/drug effects
- Testis/drug effects*
- Testis/ultrastructure
- Zebrafish
- PubMed
- 34175825 Full text @ Ecotoxicol. Environ. Saf.
- CTD
- 34175825
Citation
Wu, Z., Wang, F., Hu, L., Zhang, J., Chen, D., Zhao, S. (2021) Inhibition of endoplasmic reticulum stress-related autophagy attenuates MCLR-induced apoptosis in zebrafish testis and mouse TM4 cells. Ecotoxicology and environmental safety. 221:112438.
Abstract
Microcystin-leucine arginine (MCLR), a widespread environmental contaminant produced by cyanobacteria, poses a severe threat to the male reproductive system. However, the mechanisms of MCLR-induced testis injury accompanied by autophagy are still obscure. This study aimed to investigate the effects of MCLR on autophagy and apoptosis on the male reproductive system and its mechanism both in vitro and in vivo. MCLR caused damage to the testis of zebrafish, resulting in decreased hatching and growth retardation in the offspring. It also remarkably enhanced autophagic flux by elevating the expression of LC3BII, ATG5, and ATG12 proteins. The autophagic flux was also confirmed through the formation of autophagosomes in the ultrastructure of the zebrafish testis and the accumulation of LC3-positive puncta in zebrafish testis and mouse TM4 cells. Further evaluations revealed that inhibition of autophagy by 3-methyladenine (3-MA) significantly attenuated MCLR-induced apoptosis. This finding indicated that autophagy plays an essential role in cell death in the male reproductive system. Besides, inhibiting endoplasmic reticulum (ER) stress using 4-phenylbutyrate (4-PBA) remarkably blocked autophagy and partially suppressed apoptosis in TM4 cells induced by MCLR. This phenomenon suggested that ER stress-related autophagy was involved in MCLR-induced apoptosis. This study reveals crosstalk between ER stress and autophagy via the PERK/eIF2α/ATF4 signaling pathway. It further suggests that ER stress-related autophagy contributes to MCLR-induced apoptosis and injury in the male reproductive system. These findings provide a novel insight into MCLR-induced impairments of the testis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping