2016
DOI: 10.1016/j.freeradbiomed.2016.11.007
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Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage

Abstract: Rationale Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. Objective To determine whether transgenic mice that express mitoc… Show more

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Cited by 75 publications
(83 citation statements)
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“…3 C , D ), which we infer preserves AEC mtDNA integrity. Third, our findings that demonstrate increased AEC MnSOD K68 acetylation, a well‐established marker of SIRT3 deficiency (33, 35), provide a role for increased mitochondrial ROS in mediating AEC mtDNA damage and apoptosis in patients with IPF and asbestosis (7, 8, 10), which is in accordance with existing data that demonstrate the pathogenic role of mtROS in asbestos‐ and bleomycin‐induced AEC injury and apoptosis (44, 68, 69).…”
Section: Discussionsupporting
confidence: 91%
“…3 C , D ), which we infer preserves AEC mtDNA integrity. Third, our findings that demonstrate increased AEC MnSOD K68 acetylation, a well‐established marker of SIRT3 deficiency (33, 35), provide a role for increased mitochondrial ROS in mediating AEC mtDNA damage and apoptosis in patients with IPF and asbestosis (7, 8, 10), which is in accordance with existing data that demonstrate the pathogenic role of mtROS in asbestos‐ and bleomycin‐induced AEC injury and apoptosis (44, 68, 69).…”
Section: Discussionsupporting
confidence: 91%
“…Mitochondria is a major source of ROS in cells [59][60][61] and uncontrolled, excessive ROS generation in the mitochondrial matrix can cause mtDNA damage, cytosol-mitochondrial calcium imbalance, and the uncoupling of the electron transport chain [40,[59][60][61][62]. Uncontrolled mtROS causes the epithelial cell damage seen in IPF [63] and asbestos-induced lung fibrosis [57,[64][65][66]. mtROS has been shown to be critical for hypoxia-induced alveolar epithelial-mesenchymal transition [67], and TGF-β induces senescence in the lung epithelial cells by the upregulation of mtROS [68], suggesting a key role for it in the alveolar epithelial cell EMT and senescence.…”
Section: Discussionmentioning
confidence: 99%
“…AMPK agonists that can indirectly activate PGC1-α, or bezafibrate (a PPAR agonist), have been used to stimulate mitochondrial biogenesis and mediate protective effects in myopathy and neurodegenerative disease models associated with mitochondrial dysfunction (157,158). For instance, a transgenic mouse model of mitochondrial catalase mediates protection against asbestos, and bleomycin induced lung fibrosis associated with prevention of mitochondrial DNA damage (159). Hexafluoro, a novel honokiol derivative, has been shown to induce SIRT3 expression in lung fibroblasts and protect from TGF-β-mediated SIRT3 depletion and ameliorate bleomycin-induced lung fibrosis in mice (90).…”
Section: Perspective On Aging Regulation In Ipf Pathology and Treatmentmentioning
confidence: 99%