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KMID : 0383820120730050258
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Tuberculosis and Respiratory Diseases
2012 Volume.73 No. 5 p.258 ~ p.265
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Inhibition of Vitamin D Receptor Translocation by Cigarette Smoking Extracts
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Uh Soo-Taek
Koo So-My
Kim Yang-Ki
Kim Ki-Up
Park Sung-Woo
Jang An-Soo
Kim Do-Jin
Kim Yong-Hoon
Park Choon-Sik
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Abstract
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Background: Vitamin D can translocate a vitamin D receptor (VDR) from the nucleus to the cell membranes. The meaning of this translocation is not elucidated in terms of a role in pathogenesis of chronic obstructive pulmonary disease (COPD) till now. VDR deficient mice are prone to develop emphysema, suggesting that abnormal function of VDR might influence a generation of COPD. The blood levels of vitamin D have known to be well correlated with that of lung function in patients with COPD, and smoking is the most important risk factor in development of COPD. This study was performed to investigate whether cigarette smoke extracts (CSE) can inhibit the translocation of VDR and whether mitogen activated protein kinases (MAPKs) are involved in this inhibition.
Materials and Methods: Human alveolar basal epithelial cell line (A549) was used in this study. 1,25-(OH2)D3 and/or MAPKs inhibitors and antioxidants were pre-incubated before stimulation with 10% CSE, and then nucleus and microsomal proteins were extracted for a Western blot of VDR.
Results: Five minutes treatment of 1,25-(OH2)D3 induced translocation of VDR from nucleus to microsomes by a dose-dependent manner. CSE inhibited 1,25-(OH2)D3-induced translocation of VDR in both concentrations of 10% and 20%. All MAPKs inhibitors did not suppress the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR. Quercetin suppressed the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR, but not in n-acetylcysteine.
Conclusion: CSE has an ability to inhibit vitamin D-induced VDR translocation, but MAPKs are not involved in this inhibition.
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KEYWORD
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Vitamin D, Receptors, Calcitriol, Extracelular Signal-Regulated MAP Kinases, Antioxidants, Pulmonary Disease, Chronic Obstructive
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