Melatonin alleviates cigarette smoke-induced endothelial cell pyroptosis through inhibiting ROS/NLRP3 axis
Autor: | Changwei Liu, Leng Ni, Rui Zhang, Xuebin Wang, Baitao Ma, Xudong Liu, Zhewei Zhao, Rong Zeng, Xitao Song, Ye Bian |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cell Survival Biophysics Pharmacology medicine.disease_cause Biochemistry Antioxidants Cigarette Smoking Rats Sprague-Dawley Melatonin 03 medical and health sciences chemistry.chemical_compound Pineal gland 0302 clinical medicine Downregulation and upregulation NLR Family Pyrin Domain-Containing 3 Protein Pyroptosis medicine Animals Humans Propidium iodide Receptor Molecular Biology Cells Cultured integumentary system Endothelial Cells Cell Biology Rats Endothelial stem cell Oxidative Stress 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Reactive Oxygen Species Oxidative stress medicine.drug |
Zdroj: | Biochemical and Biophysical Research Communications. 519:402-408 |
ISSN: | 0006-291X |
Popis: | Endothelial dysfunction (ED) is a crucial and initial stage for the development of cardiovascular diseases. Accumulated evidence has demonstrated causative links between cigarette smoke (CS) and ED. However, the underlying mechanisms remain largely unknown. Pyroptosis is a unique form of inflammatory cell death. In this study, we found that cigarette smoke extract (CSE) increased pyroptosis in endothelial cells (ECs) as evidenced by increasing lactate dehydrogenase release and the number of propidium iodide (PI) positive cells. A specific NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inhibitor (MCC950) pretreatment dramatically reduced CSE-induced pyroptosis. Additionally, we also observed that N-Acetylcysteine (NAC, a ROS scavenger) pretreatment inhibited NLRP3 inflammasome activation as evidenced by suppressing the upregulation of NLRP3, ASC, cleaved-caspase-1, GSDMD-N, IL-1β and IL-18 protein levels in CSE-treated ECs. Meanwhile, NAC pretreatment also remarkably inhibited CSE-induced EC pyroptosis. Melatonin is a hormone synthesized and secreted by mammalian pineal gland and plays a protective role in various cardiovascular diseases through its powerful anti-inflammatory and antioxidant properties. In this study, melatonin was observed to inhibit ROS production, NLRP3 inflammasome activation and pyroptosis in CSE-treated ECs. Moreover, oxidative stress and NLRP3 inflammasome activation in carotid arteries of smoking rats was also inhibited by melatonin. In conclusion, our study generated two novel findings, (i) CS activates ROS/NLRP3 axis and induces EC pyroptosis; (ii) melatonin attenuates CS-induced EC pyroptosis by inhibiting ROS/NLRP3 axis. |
Databáze: | OpenAIRE |
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