Mitochondrial dysfunction in the aged lung and COPD: A role for mitochondrial calcium?
| Autor: | R Choo-Wing, O Bonneau, K Choy, D Rowlands, Salil Srivastava, A Martinez Ledo, M Morris, K Subramanian, T Shavlakadze |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
COPD Lung Mucociliary clearance Superoxide business.industry medicine.disease respiratory tract diseases Pathogenesis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology medicine.anatomical_structure 030228 respiratory system chemistry Downregulation and upregulation Internal medicine medicine Gene silencing Phosphorylation 030212 general & internal medicine business |
| Zdroj: | 03.02 - Airway cell biology and immunopathology. |
| DOI: | 10.1183/23120541.lsc-2020.36 |
| Popis: | Mitochondrial dysfunction contributes to the pathogenesis of lung aging and chronic obstructive pulmonary disease (COPD), however the underlying mechanisms remain poorly understood. In a rat model of lung aging, RNA sequencing of lung tissue revealed a downregulation in genes related to mitochondrial oxidative phosphorylation and Ca2+ signaling. Increased protein expression of mitochondrial calcium uniporter (MCU) was detected in the lungs of aged rats and COPD patients, further supporting the role of mitochondrial Ca2+ mediated dysfunction. Using an in vitro model of COPD, exposure of the immortalized bronchial epithelial cell line Beas2B, to cigarette smoke extract (CSE, 5%, 6h) increased mitochondrial Ca2+ loading. Notably, silencing of MCU in primary human bronchial epithelial cells exposed to CSE significantly reduced the loss of mitochondrial membrane potential and generation of mitochondrial derived superoxide, demonstrating a role for MCU mediated mitochondrial dysfunction. Mucus hypersecretion is a hallmark of COPD, which suggests impaired mucociliary clearance (MCC). Incubation of ex vivo murine tracheal strips with antimycin A (1μM, 1h), a mitochondrial complex III inhibitor, demonstrated a reduction in fluorescent bead displacement as a measure of MCC (P |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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