Abstract | OBJECTIVES: The purpose of this study was to investigate the effect of roxithromycin on apoptosis of airway smooth muscle cells (ASMCs) from a rat model of asthma and uncover signaling pathway underlying the cytotoxicity of roxithromycin. MATERIALS AND METHODS: ASMCs were isolated from a rat model of asthma and treated with or without roxithromycin for 48 h before parameter detection. Cell viability was assessed by WST-8 assay and flow cytometry after Annexin V/PI double staining. Changes in the mitochondrial membrane potential (ΔΨm) were measured by flow cytometry using JC-1. Cytochrome C (Cyt c), cleaved Caspase-9/3 and P27 were evaluated by Western Blot. RESULTS: Incubation with roxithromycin reduced ASMCs proliferation and enhanced apoptosis in a dose-dependent manner. Flow cytometry revealed a loss of ΔΨm and Western Blot displayed Caspase-9/3 activation as well as Cyt c release from mitochondria to the the cytosol after the treatment of roxithromycin. In addition, P27 were more strongly expressed in AMSCs treated with roxithromycin compared with the control group. CONCLUSIONS:
Roxithromycin induced apoptosis of ASMCs derived from a rat model of asthma in a dose-dependent manner via a caspase-3- and caspase-9-dependent mitochondrial pathway, involving the up-regulation of P27.
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Authors | Y-R Dai, H-Y Wu, L-Q Wu, H Xu, J Yin, S-S Yan, W-X Zeng |
Journal | European review for medical and pharmacological sciences
(Eur Rev Med Pharmacol Sci)
Vol. 18
Issue 23
Pg. 3564-72
( 2014)
ISSN: 2284-0729 [Electronic] Italy |
PMID | 25535124
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Apoptosis
(drug effects, physiology)
- Asthma
(drug therapy, metabolism, pathology)
- Cell Proliferation
(drug effects, physiology)
- Cell Survival
(drug effects, physiology)
- Cells, Cultured
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Myocytes, Smooth Muscle
(drug effects, metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
- Roxithromycin
(therapeutic use, toxicity)
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