Oxidative Stress Mediates Microcystin-LR-Induced Endoplasmic Reticulum Stress and Autophagy in KK-1 Cells and C57BL/6...

Area of Science:

• Environmental Toxicology
• Cell Biology
• Reproductive Toxicology

Background:

• Cyanobacteria produce microcystin-leucine arginine (MC-LR), a toxin with known reproductive toxicity.
• The specific mechanisms linking MC-LR to female reproductive system damage, particularly involving oxidative stress, endoplasmic reticulum stress (ERs), and autophagy, remain largely unexplored.

Purpose of the Study:

• To investigate the molecular pathways through which MC-LR induces oxidative stress, ERs, and autophagy in the female reproductive system.
• To evaluate the protective effects of N-acetyl-l-cysteine (NAC) against MC-LR-induced toxicity.

Main Methods:

• Murine ovarian granular cells (KK-1) and C57BL/6 mice were exposed to varying concentrations of MC-LR, with or without NAC.
• Key markers of oxidative stress (ROS), ER stress (PERK, GRP78, XBP1, CHOP), and autophagy (ATG12, ATG5, ATG16, Beclin1) were quantified.

Main Results:

• MC-LR induced apoptosis and morphological changes in ovarian cells and tissues.
• MC-LR significantly increased reactive oxygen species (ROS) generation and depleted antioxidant capacity.
• MC-LR upregulated key proteins involved in ER stress and autophagy via PERK/ATG12 and XBP1/Beclin1 pathways.
• NAC pretreatment partially reversed MC-LR-induced ER stress and autophagy.

Conclusions:

• Oxidative stress is a critical mediator of MC-LR-induced endoplasmic reticulum stress and autophagy in ovarian cells and tissues.
• MC-LR toxicity to the female reproductive system is significantly influenced by oxidative stress.
• NAC demonstrates potential as a protective agent against MC-LR-induced reproductive toxicity.