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- W2324025216 abstract "Amiodarone (AD) is an anti-arrhythmic drug with very well-known vasodilatory properties. Severe pulmonary toxicity has been reported in patients receiving AD even at low doses, with the most common histological finding being chronic interstitial pneumonia. The precise mechanism underlying AD-induced pulmonary toxicity remains unknown. Dysfunctional mitochondria and enhanced oxidative stress via the production of reactive oxygen species (ROS) have been reported in AD-induced pulmonary toxicity. Recent unpublished studies from our group revealed AECII (Alveolar epithelial cells type II) specific autophagy alongside with AECII apoptosis and lysosomal stress in the lungs of AD treated mice and mouse lung epithelial (MLE) 12 cells. This convinced us to hypothesize that AD alters mitochondrial autophagy (mitophagy) and causes subsequent cell death, as an outcome of increased oxidative stress. Apart from the well-known autophagy markers like LC3BII, p62, ATG7, ATG12 – 5, important mitophagy markers like Pink and NIX/BNIP3L was significantly increased in AD treated mice lungs. In addition, PUMA, Bax and Cytochrome C, which are involved in mitochondrial dysregulation, were also elevated in response to AD treatment in mice lungs and in AECII. Hemeoxygenase-1 (HO-1), a pivotal antioxidant protein was increased in AD treated mice lungs, AECII and MLE12 cells. Since HO-1 forms a major link between oxidative stress and autophagy, we hypothesized that AD induced autophagy might be HO-1 dependent. In contrast, both in vitro knockdown (via siRNA) and chemical inhibition of HO-1 increased the levels of LC3BII. Similarly, LCB knockdown further increased the AD induced HO-1 protein levels in MLE12 cells. This indicates that AD induces HO-1 independent autophagy and HO-1 seems to be protective in function. We conclude that amiodarone induces mitochondrial autophagy, which might accelerate the apoptosis of AECII and thereby lung fibrosis in response to amiodarone treatment." @default.
- W2324025216 created "2016-06-24" @default.
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- W2324025216 date "2014-06-10" @default.
- W2324025216 modified "2023-09-23" @default.
- W2324025216 title "Mitochondrial autophagy in the development of amiodarone induced pulmonary fibrosis" @default.
- W2324025216 doi "https://doi.org/10.1055/s-0034-1376803" @default.
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