Targeting mitochondrial reactive oxygen species alleviates allergic airway disease in a mouse model of obese allergic asthma

ABSTRACT: Obesity is associated with severe, difficult to control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment strategy. Using a mouse model of house dust mite (HDM) induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ); we investigated the effects of obesity and mROS on airway inflammation, remodelling and airway hyperreactivity (AHR). HDM induces airway inflammation, remodelling and hyperreactivity in both lean and obese mice. Obese allergic mice showed increased lung tissue eotaxin levels, airway tissue eosinophilia and AHR when compared to lean allergic mice. MitoQ reduced markers of airway inflammation, remodelling and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obeseHDM mice. mROS regulates cell signalling by protein oxidation of multiple downstream targets: MitoQ reduced HDM-induced cysteine-sulfenylation of several proteins including those involved in the unfolded protein response (UPR). In summary, mROS mediates the development of allergic airway disease and hence MitoQ might be effective for the treatment for asthma, and specific features of obese asthma.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Bos Taurus (bovine) Mus Musculus (mouse)

TISSUE(S): Lung

DISEASE(S): Allergic Asthma

SUBMITTER: Ying Wai Lam  

LAB HEAD: Vikas Anathy

PROVIDER: PXD029715 | Pride | 2023-06-02

REPOSITORIES: Pride