Nicotine affects mitochondrial structure and function in human airway smooth muscle cells

Area of Science:

• Cellular Biology
• Respiratory Medicine
• Pharmacology

Background:

• Asthma is worsened by smoking, with nicotine as a key component.
• Nicotine acts via nicotinic acetylcholine receptors (nAChRs), particularly α7nAChR, affecting airway dynamics.
• Mitochondria regulate airway smooth muscle tone and cellular stress, but their role in nicotine's effects on asthma is unknown.

Purpose of the Study:

• To investigate how nicotine affects mitochondrial structure and function in asthmatic airway smooth muscle (ASM).
• To determine the role of α7nAChR in nicotine-induced mitochondrial changes in ASM.
• To explore the impact of nicotine on mitochondrial calcium ([Ca2+]m) and bioenergetics in asthma.

Main Methods:

• Used human ASM (hASM) cells from nonasthmatics, asthmatics, and smokers.
• Examined nicotine's effects on mitochondrial dynamics, morphology, and [Ca2+]m using fluorescence imaging.
• Assessed mitochondrial respiration and bioenergetics via Seahorse analysis.
• Utilized α7nAChR siRNA to confirm receptor involvement.

Main Results:

• Nicotine (10 μM) robustly increased [Ca2+]m, especially in asthmatic and smoker cells.
• Nicotine altered mitochondrial dynamics by increasing fission and decreasing fusion proteins in asthmatics and smokers.
• Nicotine impaired oxidative phosphorylation parameters, with blunted responses in asthmatics and smokers.
• α7nAChR inhibition reversed nicotine-induced mitochondrial dysfunction.

Conclusions:

• Mitochondria are a significant target of nicotine's effects in ASM cells.
• Nicotine disrupts mitochondrial structure, calcium handling, and energy production in asthma.
• Targeting α7nAChR-mediated mitochondrial dysfunction may offer new therapeutic strategies for asthma exacerbated by smoking.