期刊
TOXICOLOGICAL SCIENCES
卷 183, 期 2, 页码 352-362出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfab087
关键词
sodium tanshinone IIA sulfonate; alveolar epithelial cells; apoptosis; mitochondrial dysfunction; oxidative stress; sirtuin 1
类别
资金
- National Natural Science Foundation of China [81770043, 81800072, 81520108001]
- National Key RD Project [2016YFC0903700]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01S155]
- Natural Science Foundation of Guangdong Province [2018A030310291, 2016A030311020, 2018A030310290, 2016A030313606]
- Guangzhou Municipal Science and Technology [201607020030, 201804010052]
- Changjiang Scholars and Innovative Research Team in University [IRT0961]
Sodium tanshinone IIA sulfonate (STS) attenuates cigarette smoke (CS)-induced alveolar epithelial cell (AEC) apoptosis by enhancing mitochondrial function and reducing oxidative stress through the SIRT1 pathway.
Emphysema is one of the most important phenotypes for chronic obstructive pulmonary disease (COPD). Apoptosis in alveolar epithelial cells (AECs) causes the emphysematous alterations in the smokers and patients with COPD. Sirtuin 1 (SIRT1) is able to attenuate mitochondrial dysfunction, oxidative stress, and to modulate apoptosis. It has been shown that sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, protects against cigarette smoke (CS)-induced emphysema/COPD in mice. However, the mechanisms underlying these findings remain unclear. Here, we investigate whether and how STS attenuates AEC apoptosis via a SIRT1-dependent mechanism. We found that STS treatment decreased CS extract (CSE)-induced apoptosis in human alveolar epithelial A549 cells. STS reduced oxidative stress, improved mitochondrial function and mitochondrial membrane potential (Delta Psi(m)), and restored mitochondrial dynamics-related protein expression. Moreover, STS promoted mitophagy, and increased oxidative phosphorylation protein levels (complexes I-IV) in CSE-stimulated A549 cells. The protective effects of STS were associated with SIRT1 upregulation, because SIRT1 inhibition by EX 527 significantly attenuated or abolished the ability of STS to reverse the CSE-induced mitochondrial damage, oxidative stress, and apoptosis in A549 cells. In conclusion, STS ameliorates CSE-induced AEC apoptosis by improving mitochondrial function and reducing oxidative stress via enhancing SIRT1 pathway. These findings provide novel mechanisms underlying the protection of STS against CS-induced COPD.
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