Involvement of B-cell CLL/lymphoma 2 promoter methylation in cigarette smoke extract-induced emphysema. Issue 8 (April 2016)

• Record Type: Journal Article
• Authors: Zeng, Huihui; Shi, Zhihui; Kong, Xianglong; Chen, Yan; Zhang, Hongliang; Peng, Hong; Luo, Hong; Chen, Ping
• Is Part Of: Experimental biology and medicine. Volume 241:Issue 8(2016)
• Page Start: 808
• Page End: 816
• Publication Date: 2016-04
• Subjects: Apoptosis -- B-cell CLL/lymphoma 2 -- emphysema -- methylation; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370216635759
• Languages: English
• ISSNs: 1535-3702

Abstract

Abnormal apoptotic events play an important role in the pathogenesis of emphysema. The B-cell CLL/lymphoma 2 (Bcl-2) family proteins are essential and critical regulators of apoptosis. We determined whether the anti-apoptotic Bcl-2 play a role in the cigarette smoke extract (CSE)-induced emphysema. Furthermore, given the involvement of epigenetics in chronic obstructive pulmonary disease, we hypothesized that the deregulation of Bcl-2 might be caused by gene methylation. The emphysema in BALB/C mice was established by intraperitoneally injection of CSE. 5-aza-2′-deoxycytidine (AZA; a demethylation reagent) and phosphate-buffered saline were also administered intraperitoneally as CSE. TUNEL assay was used to assess apoptotic index of pulmonary cells. The methylation status of CpG dinucleotides within the Bcl-2 promoter was observed in all groups by bisulfite sequencing PCR. Pulmonary expression of Bcl-2, Bax, and cytochrome C were measured after four weeks of treatment. The apoptotic index of pulmonary cells in CSE injection group was much higher than control ((25.88 ± 7.55)% vs . (6.28 ± 2.96)%). Compared to control mice, decreased expression of Bcl-2 and high methylation of Bcl-2 promoter was observed in CSE injected mice (0.88 ± 0.08 vs . 0.49 ± 0.11, (3.82 ± 1.34)% vs . (35.68 ± 5.99)%, P < 0.01).CSE treatment induced lung cell apoptosis and decreased lung function. AZA treatment increased Bcl-2 expression with Bcl-2 promoter demethylation. AZA also alleviated the lung cell apoptosis and function failure caused by CSE treatment. The decreased expression of anti-apoptotic Bcl-2 might account for the increased apoptosis in CSE induced-emphysema. Apparently, epigenetic alternation played a role in this deregulation of Bcl-2 expression, and it might support the involvement of epigenetic events in the pathogenesis of emphysema.