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Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2013 Nov 15; Vol. 305 (10), pp. L737-46. Date of Electronic Publication: 2013 Sep 20. - Publication Year :
- 2013
-
Abstract
- Mitochondria are dynamic organelles that continuously change their shape through fission and fusion. Disruption of mitochondrial dynamics is involved in disease pathology through excessive reactive oxygen species (ROS) production. Accelerated cellular senescence resulting from cigarette smoke exposure with excessive ROS production has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Hence, we investigated the involvement of mitochondrial dynamics and ROS production in terms of cigarette smoke extract (CSE)-induced cellular senescence in human bronchial epithelial cells (HBEC). Mitochondrial morphology was examined by electron microscopy and fluorescence microscopy. Senescence-associated β-galactosidase staining and p21 Western blotting of primary HBEC were performed to evaluate cellular senescence. Mitochondrial-specific superoxide production was measured by MitoSOX staining. Mitochondrial fragmentation was induced by knockdown of mitochondrial fusion proteins (OPA1 or Mitofusins) by small-interfering RNA transfection. N-acetylcysteine and Mito-TEMPO were used as antioxidants. Mitochondria in bronchial epithelial cells were prone to be more fragmented in COPD lung tissues. CSE induced mitochondrial fragmentation and mitochondrial ROS production, which were responsible for acceleration of cellular senescence in HBEC. Mitochondrial fragmentation induced by knockdown of fusion proteins also increased mitochondrial ROS production and percentages of senescent cells. HBEC senescence and mitochondria fragmentation in response to CSE treatment were inhibited in the presence of antioxidants. CSE-induced mitochondrial fragmentation is involved in cellular senescence through the mechanism of mitochondrial ROS production. Hence, disruption of mitochondrial dynamics may be a part of the pathogenic sequence of COPD development.
- Subjects :
- Blotting, Western
Bronchi drug effects
Bronchi metabolism
Cells, Cultured
Dynamins
Epithelial Cells drug effects
Epithelial Cells metabolism
GTP Phosphohydrolases antagonists & inhibitors
GTP Phosphohydrolases genetics
GTP Phosphohydrolases metabolism
Humans
Immunoenzyme Techniques
Membrane Proteins antagonists & inhibitors
Membrane Proteins genetics
Membrane Proteins metabolism
Microscopy, Electron
Microtubule-Associated Proteins antagonists & inhibitors
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Mitochondria drug effects
Mitochondria metabolism
Mitochondrial Proteins antagonists & inhibitors
Mitochondrial Proteins genetics
Mitochondrial Proteins metabolism
RNA, Small Interfering genetics
Bronchi pathology
Cellular Senescence drug effects
Epithelial Cells pathology
Mitochondria pathology
Reactive Oxygen Species metabolism
Nicotiana adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 305
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24056969
- Full Text :
- https://doi.org/10.1152/ajplung.00146.2013