Copper oxide nanoparticles induce pulmonary inflammation via triggering cellular cuproptosis

Area of Science:

• Environmental Toxicology
• Nanomaterial Safety
• Cellular Biology

Background:

• Copper oxide nanoparticles (CuO NPs) are widely used industrially.
• Concerns exist regarding CuO NP toxicity, particularly pulmonary effects.
• The precise mechanisms of CuO NP-induced lung inflammation remain unclear.

Purpose of the Study:

• To investigate CuO NP-induced pulmonary inflammation and its underlying mechanism.
• To explore the role of cellular cuproptosis in CuO NP toxicity.
• To elucidate the specific molecular pathways involved.

Main Methods:

• Exposure of C57BL/6 mice and MH-S cells to CuO NPs via intratracheal instillation.
• Histopathological examination of lung tissues.
• Measurement of intracellular copper levels and cuproptosis markers (FDX1, DLST, DLAT, CTR1).
• Transcript sequencing and metabolomics analysis.
• Interference with FDX1 expression.

Main Results:

• CuO NPs induced significant pulmonary inflammation in mice.
• Intracellular Cu2+ levels and cuproptosis indicators were elevated in lung tissues and cells.
• Transcriptomic and metabolomic data confirmed CuO NP-induced cuproptosis and inflammation.
• Interleukin-17A (IL-17A) levels increased during CuO NP-induced cuproptosis.
• FDX1 interference mitigated cuproptosis and IL-17A release.

Conclusions:

• CuO NPs trigger pulmonary inflammation through FDX1-mediated cuproptosis.
• Intracellular copper accumulation and cuproptosis pathway activation are key mechanisms.
• This study reveals a novel cuproptosis-driven pathway for CuO NP respiratory toxicity.