Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells

Area of Science:

• Environmental Health
• Toxicology
• Neuroscience

Background:

• Growing evidence links air pollutants, particularly particulate matter (PM), to adverse central nervous system effects.
• Oxidative stress and inflammation are known consequences of PM exposure, but the precise mechanisms remain unclear.
• The olfactory system is a potential pathway for PM entry into the brain, yet its response to air pollutants is not well understood.

Purpose of the Study:

• To investigate the effects of urban size-segregated PM on primary human olfactory mucosal (hOM) cells.
• To elucidate the role of neuronal pentraxin 1 (NPTX1) in mediating cellular responses to PM exposure.

Main Methods:

• Exposure of primary hOM cells to urban size-segregated PM.
• Assessment of metabolic activity, inflammatory response (cytometric bead array), oxidative stress, apoptosis (caspase-3/7 activity), and mitochondrial function.
• RNA sequencing to identify gene expression changes, followed by targeted gene suppression (NPTX1).

Main Results:

• PM exposure reduced metabolic activity and induced mild inflammation, oxidative stress, and mitochondrial dysfunction in hOM cells.
• NPTX1 was identified as upregulated in PM-exposed cells and its suppression exacerbated PM-induced mitochondrial defects.
• PM exposure led to increased caspase-3/7 activity and perturbed mitochondrial membrane potential, indicating early apoptosis and mitochondrial damage.

Conclusions:

• Urban PM exposure perturbs key mitochondrial functions in hOM cells through a mechanism involving NPTX1.
• Inflammatory responses and early apoptosis accompany PM-induced mitochondrial dysfunction.
• Findings enhance understanding of PM's harmful effects on human health and inform air pollution mitigation strategies.