mitoquinone and Asthma

Multiple studies have determined that obesity increases asthma risk or severity. Metabolic changes of obesity, such as diabetes or insulin resistance, are associated with asthma and poorer lung function. Insulin resistance is also found to increase asthma risk independent of body mass. Conversely, asthma is associated with abnormal glucose and lipid metabolism, insulin resistance, and obesity. Here we review our current understanding of how dietary and lifestyle factors lead to changes in mitochondrial metabolism and cellular bioenergetics, inducing various components of the cardiometabolic syndrome and airway disease.

Topics: Asthma; Bronchial Hyperreactivity; Caloric Restriction; Energy Metabolism; Exercise; Humans; Metabolic Syndrome; Mitochondria; Molecular Targeted Therapy; Obesity; Organophosphorus Compounds; Ubiquinone

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 in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. 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 ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway inflammation, remodeling, and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP

Topics: Animals; Asthma; Disease Models, Animal; Eosinophilia; Inflammation; Lung; Obesity; Pyroglyphidae

Mitochondrial dysfunction is an essential part of the pathophysiology of asthma, and potential treatments that target the malfunctioning mitochondria have attracted widespread attention. We have previously demonstrated that aberrant epithelial β-catenin signaling played a crucial role in a toluene diisocyanate (TDI)-induced steroid-insensitive asthma model. The objective of this study was to determine if the mitochondrially targeted antioxidant mitoquinone(MitoQ) regulated the activation of β-catenin in TDI-induced asthma.. Mice were sensitized and challenged with TDI to generate a steroid-insensitive asthma model. Human bronchial epithelial cells (16HBE) were exposed to TDI-human serum albumin (HSA) and ethidium bromide(EB) to simulate the TDI-induced asthma model and mitochondrial dysfunction.. MitoQ dramatically attenuated TDI-induced AHR, airway inflammation, airway goblet cell metaplasia, and collagen deposition and markedly protected epithelial mitochondrial functions by preserving mass and diminishing the production of reactive oxygen species (ROS). MitoQ administration stabilized β-catenin destruction complex from disintegration and inhibited the activation of β-catenin. Similarly, YAP1, an important constituent of β-catenin destruction complex, was inhibited by Dasatinib, which alleviated airway inflammation and the activation of β-catenin, and restored mitochondrial mass. In vitro, treating 16HBE cells with EB led to the activation of YAP1 and β-catenin signaling, decreased the expression of glucocorticoid receptors and up-regulated interleukin (IL)-1β, IL6 and IL-8 expression.. Our results indicated that mitochondria mediates airway inflammation by regulating the stability of the β-catenin destruction complex and MitoQ might be a promising therapeutic approach to improve airway inflammation and severe asthma.. The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Topics: Animals; Asthma; beta Catenin; Disease Models, Animal; Humans; Inflammation; Mice; Mice, Inbred BALB C; Organophosphorus Compounds