Peroxinredoxin 6 reduction accelerates cigarette smoke extract‑induced senescence by regulating autophagy in BEAS‑2B cells.
Peroxinredoxin 6 reduction accelerates cigarette smoke extract‑induced senescence by regulating autophagy in BEAS‑2B cells.
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DOI：
10.3892/etm.2023.12074
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发表时间：
2023-08
影响因子：
2.7
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Luo J;Wang X;Wei T;Lang K;Bao C;Yang D
香烟烟雾（CS）诱导的加速衰老和自噬不足与慢性阻塞性肺疾病（COPD）的发病机制有关。Peroxiredoxin（PRDX）6是一种具有普遍抗氧化能力的蛋白质。先前的研究表明，PRDX 6可以激活自噬并减轻其他疾病的衰老。本研究调查了PRDX 6调节的自噬是否参与CS提取物（CSE）诱导的BEAS-2B细胞衰老的调节，通过敲低PRDX 6表达。此外，本研究通过分析来自Gene Expression Omnibus数据库的GSE 20257数据集，评估了COPD患者小气道上皮中PRDX 6、自噬和衰老相关基因的mRNA水平。结果表明，CSE降低PRDX 6表达水平，并瞬时诱导自噬激活，随后加速BEAS-2B细胞的衰老。在CSE处理的BEAS-2B细胞中，PRDX 6的敲低诱导自噬降解并加速衰老。此外，在CSE处理的BEAS-2B细胞中，通过3-甲基腺嘌呤的自噬抑制增加了P16和P21的表达水平，而通过雷帕霉素的自噬激活降低了P16和P21的表达水平。GSE 20257数据集显示，与非吸烟者相比，COPD患者的PRDX 6、sirtuin（SIRT）1和SIRT 6 mRNA水平较低，P62和P16 mRNA水平较高。P62 mRNA与P16、P21和SIRT 1显著相关，表明自噬清除受损蛋白不足可能参与了COPD细胞衰老的加速。总之，本研究证明了PRDX 6在COPD中的新保护作用。此外，PRDX 6的减少可以通过诱导CSE处理的BEAS-2B细胞中的自噬损伤来加速衰老。
Cigarette smoke (CS)-induced accelerated senescence and insufficient autophagy has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Peroxiredoxin (PRDX) 6 is a protein with prevalent antioxidant capacity. Previous studies indicate that PRDX6 could activate autophagy and alleviate senescence in other diseases. The present study investigated whether PRDX6-regulated autophagy was involved in the regulation of CS extract (CSE)-induced BEAS-2B cell senescence via the knockdown of PRDX6 expression. Furthermore, the present study evaluated the mRNA levels of PRDX6, autophagy and senescence-associated genes in the small airway epithelium from patients with COPD by analyzing the GSE20257 dataset from the Gene Expression Omnibus database. The results demonstrated that CSE reduced PRDX6 expression levels and transiently induced the activation of autophagy, followed by the accelerated senescence of BEAS-2B cells. Knockdown of PRDX6 induced autophagy degradation and accelerated senescence in CSE-treated BEAS-2B cells. Furthermore, autophagy inhibition by 3-Methyladenine increased P16 and P21 expression levels, while autophagy activation by rapamycin reduced P16 and P21 expression levels in CSE-treated BEAS-2B cells. The GSE20257 dataset revealed that patients with COPD had lower PRDX6, sirtuin (SIRT) 1 and SIRT6 mRNA levels, and higher P62 and P16 mRNA levels compared with non-smokers. P62 mRNA was significantly correlated with P16, P21 and SIRT1, which indicated that insufficient autophagic clearance of damaged proteins could be involved in accelerated cell senescence in COPD. In conclusion, the present study demonstrated a novel protective role for PRDX6 in COPD. Furthermore, a reduction in PRDX6 could accelerate senescence by inducing autophagy impairment in CSE-treated BEAS-2B cells.
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影响因子：
3.9
作者：
Hwang, Jae-woong;Chung, Sangwoon;Sundar, Isaac K.;Yao, Hongwei;Arunachalam, Gnanapragasam;McBurney, Michael W.;Rahman, Irfan
通讯作者：
Rahman, Irfan
DOI：
10.1152/ajplung.00102.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
An, Chang Hyeok;Wang, Xiao Mei;Choi, Augustine M. K.
通讯作者：
Choi, Augustine M. K.
影响因子：
4.6
作者：
Kono Y;Colley T;To M;Papaioannou AI;Mercado N;Baker JR;To Y;Abe S;Haruki K;Ito K;Barnes PJ
通讯作者：
Barnes PJ
香烟烟雾诱导的自噬损伤调节 ARPE-19 细胞中的 AMD 发病机制。
影响因子：
3.7
作者：
Govindaraju VK;Bodas M;Vij N
通讯作者：
Vij N
DOI：
10.1152/ajplung.1998.274.5.l750
发表时间：
1998-05-01
影响因子：
4.9
作者：
Kim, TS;Dodia, C;Fisher, AB
通讯作者：
Fisher, AB