Oxidative stress and cell cycle arrest induced by short-term exposure to dustfall PM_2.5 in A549 cells

Area of Science:

• Environmental Health
• Molecular Toxicology
• Cell Biology

Background:

• Particulate Matter 2.5 (PM2.5) is linked to lung diseases via inflammation, immune toxicity, oxidative stress, and genetic mutations.
• The intricate molecular mechanisms underlying PM2.5 toxicity remain incompletely understood.

Purpose of the Study:

• To investigate the cytotoxicity, oxidative damage, mitochondrial damage, apoptosis, and cell cycle arrest induced by NX and QH PM2.5 in A549 cells.
• To identify the molecular mechanisms, including gene expression changes, associated with PM2.5-induced cell cycle arrest.

Main Methods:

• Exposure of A549 cells to NX and QH PM2.5.
• Assessment of cell viability, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and mitochondrial integrity.
• Analysis of apoptosis, cell cycle distribution, and expression levels of cell cycle-related genes (p53, p21, CDK1) and lncRNA Sox2ot and EZH2.

Main Results:

• PM2.5 exposure significantly reduced A549 cell viability.
• Excessive ROS generation led to decreased MMP, damaged mitochondrial membrane integrity, and induced mitochondrial oxidative damage, resulting in apoptosis.
• PM2.5 induced G2/M phase cell cycle arrest, characterized by upregulated p53 and p21, and downregulated CDK1 mRNA expression.
• lncRNA Sox2ot was implicated in PM2.5-induced G2/M phase arrest by regulating EZH2 expression.

Conclusions:

• PM2.5 exerts cytotoxicity in A549 cells through oxidative stress and mitochondrial damage, leading to apoptosis.
• PM2.5 induces G2/M phase cell cycle arrest via modulation of p53, p21, CDK1, and potentially lncRNA Sox2ot-EZH2 pathways.
• These findings elucidate key molecular mechanisms of PM2.5 toxicity, highlighting potential therapeutic targets.