The role of DNA repair deficiency in lipid accumulation: A proof-of-concept study.

Animal models suggest an association between base excision repair (BER) deficiency and increased risk of obesity. To mechanistically investigate the effect of BER deficiency on intracellular lipid accumulation, we studied metabolic activity in in vitro BER knockdown (KD) models, targeting MutY DNA Glycosylase (MUTYH), Nth Like DNA Glycosylase 1 (NTHL1) and 8-Oxoguanine DNA Glycosylase (OGG1). We hypothesized that exposing BER deficient cells to lipids leads to reduced mitochondrial function and enhanced intracellular lipid accumulation.

Assessing toxicity of amorphous nanoplastics in airway- and lung epithelial cells using air-liquid interface models.

Background: Inhalation is one of the main exposure routes to nanoplastics. Knowledge of the toxicological impact of nanoplastics on the airway- and lung epithelium is limited and almost exclusively based on submerged in vitro models using spherical polystyrene (PS) particles.

Methods: Mono-cultures and advanced (co-)cultures of human bronchial- and alveolar epithelial cells, all air-liquid interface (ALI) cultures, were exposed to nanoplastics and reference nanoparticles.

Alterations in the molecular control of mitochondrial turnover in COPD lung and airway epithelial cells.

Abnormal mitochondria have been observed in bronchial- and alveolar epithelial cells of patients with chronic obstructive pulmonary disease (COPD). However, it is unknown if alterations in the molecular pathways regulating mitochondrial turnover (mitochondrial biogenesis vs mitophagy) are involved. Therefore, in this study, the abundance of key molecules controlling mitochondrial turnover were assessed in peripheral lung tissue from non-COPD patients (n = 6) and COPD patients (n = 11; GOLDII n = 4/11; GOLDIV n = 7/11) and in both undifferentiated and differentiated human primary bronchial epithelial cells (PBEC) from non-COPD patients and COPD patients (n = 4-7 patients/group).

Impact of sub-acute acrolein inhalation on the molecular regulation of mitochondrial metabolism in rat lung.

Nowadays, mitochondria are recognized as key players in the pathogenesis of a variety of smoking-associated lung diseases. Acrolein, a component of cigarette smoke, is a known driver of biological mechanisms underlying smoking-induced respiratory toxicity. The impact of sub-acute acrolein inhalation in vivo on key processes controlling mitochondrial homeostasis in cells of the airways however is unknown.

NF-κB-mediated metabolic remodelling in the inflamed heart in acute viral myocarditis.

Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac metabolic rewiring and if this process is driven by local inflammation.

Classical NF-κB activation impairs skeletal muscle oxidative phenotype by reducing IKK-α expression.

Background: Loss of quadriceps muscle oxidative phenotype (OXPHEN) is an evident and debilitating feature of chronic obstructive pulmonary disease (COPD). We recently demonstrated involvement of the inflammatory classical NF-κB pathway in inflammation-induced impairments in muscle OXPHEN. The exact underlying mechanisms however are unclear.

Regulation of skeletal muscle oxidative phenotype by classical NF-κB signalling.

Background: Impairments in skeletal muscle oxidative phenotype (OXPHEN) have been linked to the development of insulin resistance, metabolic inflexibility and progression of the metabolic syndrome and have been associated with progressive disability in diseases associated with chronic systemic inflammation. We previously showed that the inflammatory cytokine tumour necrosis factor-α (TNF-α) directly impairs muscle OXPHEN but underlying molecular mechanisms remained unknown. Interestingly, the inflammatory signalling pathway classical nuclear factor-κB (NF-κB) is activated in muscle in abovementioned disorders.