NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis

Area of Science:

• Neuroscience
• Cell Biology
• Toxicology

Background:

• Autophagy and apoptosis are key cell death mechanisms in pesticide neurotoxicity.
• Autophagy can protect cells by inhibiting apoptosis.
• Diquat (DQ) is a pesticide implicated in neurotoxicity.

Purpose of the Study:

• To characterize the relationship between autophagy and apoptosis in diquat-induced cell death.
• To explore autophagy regulation as a pharmacotherapeutic approach against diquat neurotoxicity.

Main Methods:

• PC12 cells were exposed to diquat (DQ).
• Cell viability, dopamine levels, apoptosis markers (caspase-3, -9, nuclear condensation), autophagy markers (LC3-II, p62), reactive oxygen species (ROS), and signaling pathways (p53, NF-κB, MAPK) were assessed.
• Inhibitors (pifithrin-α, SN50) and modulators (N-acetyl-cysteine, rapamycin, 3-methyladenine) of these pathways were used.

Main Results:

• Diquat induced concentration-dependent cytotoxicity, apoptosis, and autophagy in PC12 cells, associated with ROS production.
• Inhibitors of p53 and NF-κB reduced diquat's cytotoxicity and modulated autophagy and apoptosis.
• Autophagy induction (rapamycin) enhanced cell viability, while inhibition (3-methyladenine) increased toxicity, indicating autophagy regulates diquat-induced cell death.

Conclusions:

• Diquat-induced neurotoxicity involves complex interactions between apoptosis and autophagy.
• Autophagy modulation significantly impacts diquat's cytotoxic effects.
• Pharmacological induction of autophagy presents a potential therapeutic strategy for neurodegenerative disorders.