Phospholipidosis induced by PPARγ signaling in Human Bronchial Epithelial (BEAS-2B) Cells exposed to Amiodarone

Title
Phospholipidosis induced by PPARγ signaling in Human Bronchial Epithelial (BEAS-2B) Cells exposed to Amiodarone
Authors
송미Youn-Jung Kim류재천
Keywords
phospholipidosis; FADS2; SCD; amiodarone
Issue Date
2011-03
Publisher
Toxicological Sciences
Citation
VOL 120, NO 1, 98-108
Abstract
Phospholipidosis (PL), a disorder characterized by an accumulation of phospholipids in lysosome-derived multilamellar vesicles owing to abnormal lipid metabolism. Amiodarone (AM), an antiarrhythmic drug, can induce pulmonary PL. First, to evaluate potential mechanisms of phospholipidosis, we found lipid metabolism-–related genes by microarray. PPARG, FADS2, and SCD out of these genes were key genes in lipid metabolism and PPAR signaling by AM. The messenger RNA (mRNA) levels of PPARG, FADS2, and SCD were upregulated by AM. The PPARg antagonist GW9662 was used to investigate the possible involvement of PPARg as a mediator of AM-induced PL, and FADS2 and SCD small interfering RNAs (siRNAs) were used to examine the involvement of FADS2 and SCD in AM-induced PL. The inhibition of PPARg by GW9662 significantly attenuated the AM-induced upregulation of SCD and slightly decreased the AMinduced upregulation of FADS2. And the pretreatment of GW9662 significantly decreased the AM-induced uptake of the fluorescent phospholipid analog NBD-PC. The siRNA-mediated gene silencing of FADS2 and SCD also decreased the AM-induced NBD-PC uptake. These results suggest that the activation of the PPARg signaling pathway, including FADS2 and SCD, may play an important role in AM-induced PL. PPARG, FADS2, and SCD are AM-induced PL-related genes and may serve as potential biomarkers for PL caused by pulmonary toxicity. We also provide evidence for a possible mechanism of PL, the accumulation of phospholipid in the induction of FADS2 and SCD by PPARg, in AM-induced pulmonary toxicity.
URI
http://pubs.kist.re.kr/handle/201004/40753
ISSN
1096-6080
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE