Melatonin protects against COPD by attenuating apoptosis and endoplasmic reticulum stress via upregulating SIRT1 expression in rats

Abstract

The apoptosis of bronchial and alveolar epithelial cells plays a key role in chronic obstructive pulmonary disease (COPD). The endoplasmic reticulum (ER) stress induced by cigarette smoke contributes to apoptosis. Previous studies demonstrated that melatonin prevented the development of COPD. In addition, silent information regulator 1 (SIRT1) had a protective effect against COPD. However, it remains unclear whether SIRT1 is involved in the protection of melatonin against COPD. In this study, 32 male Wistar rats were randomly assigned to 4 groups: Control, COPD, COPD + Mel, and COPD + Mel + EX527. Rats were challenged with cigarette smoke and lipopolysaccharide with or without melatonin or EX527 (a selective inhibitor of SIRT1). The lung histopathology, apoptotic index, as well as the protein expressions of cleaved caspase-3, SIRT1, C/EBP homologous protein, and caspase-12 in the lung tissues were measured. These results demonstrated that melatonin attenuated apoptosis and ER stress in the lung tissues of rats with COPD. In addition, melatonin increased SIRT1 expression in lung tissues of rats with COPD, while inhibition of SIRT1 by EX527 upregulated ER stress and abolished the protective effect of melatonin against apoptosis. In conclusion, these findings suggested that melatonin protected against COPD by attenuating apoptosis and ER stress via upregulating SIRT1 expression in rats.

Xiaoqinglong Decoction Protects the Lungs of AECOPD Mice through the AMPK/mTOR Signaling Pathway

“…Kelsen et al [ 24 ] reported that ER stress is activated by cigarette smoke in lung tissues of patients with COPD. He et al [ 25 ] reported that inhibiting ER stress exerted protective effects against COPD by inhibiting the apoptosis of bronchial and alveolar epithelial cells. Moreover, Zhao et al [ 26 ] found that ER stress played an important role in the apoptosis of alveolar epithelial apoptosis in COPD, and adiponectin can ameliorate the progression of COPD through inhibiting the ERS-induced alveolar epithelial apoptosis in rats.…”

Melatonin’s Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease

“…Through its antioxidant and anti-inflammatory effects, melatonin is beneficial in pulmonary hypertension [ 203 , 204 , 205 ], enhances the NO-independent acetylcholine’s vasodilatory effect, decreases the systolic pressure of the right ventricle, and prevents right ventricular hypertrophy [ 206 ]. By diminishing TGF-β1 activity, apoptosis, and endoplasmic reticulum stress via Sirtuin-1 upregulation in animal studies, melatonin could be protective in chronic obstructive pulmonary disease (COPD) [ 72 , 207 ]. It also decreases dyspnea and 8-isoprostane in the exhaled air, in humans [ 208 ].…”

P53 in the impaired lungs

“…Chronic obstructive pulmonary disease (COPD) is a lung disease associated with chronic airway inflammation, which limits the airflow in the lungs. The underlying mechanisms responsible for the development of COPD involve inflammation, apoptosis, and airway epithelial remodeling [ [91] , [92] , [93] ]. It was reported that 80 % of lung cancer patients suffer from COPD [ 94 ].…”