Cigarette smoke extract-induced BEAS-2B cell apoptosis and anti-oxidative Nrf-2 up-regulation are mediated by ROS-stimulated p38 activation

Abstract

Cigarette smoke contains reactive oxygen (ROS) that can cause oxidative stress. It increases the number of apoptotic and necrotic lung cells and further induces the development of chronic airway disease. In this study, we investigated the effects of cigarette smoke extract (CSE) on apoptosis in human bronchial epithelial cells (BEAS-2B). CSE exposure induced ROS generation and p38 mitogen-activated protein kinase (MAPK) activation that are associated with the activation of apoptosis-regulating signal kinase 1 (ASK-1). N-acetylcysteine (a general antioxidant) attenuated the CSE-induced ASK-1 and p38 MAPK activation and cell apoptosis, suggesting a triggering role of ROS in ASK-1/p38 MAPK activation during apoptotic progression. In contrast, the inhibition and knockdown of p38 attenuated the expression of anti-oxidant master NF-E2-related factor 2 (Nrf-2) and CSE-induced apoptosis, suggesting that p38 MAPK modulates Nrf-2 expression and presumably prevents cell apoptosis. Taken together, the data presented in this manuscript demonstrate that the ROS-dependent ASK-1/p38 signaling cascade regulates CSE-induced BEAS-2B cell apoptosis. In addition, anti-oxidative Nrf-2 is also up-regulated by the ROS/p38 signaling cascade in this progression.

Sodium fluoride affects zebrafish behaviour and alters mRNA expressions of biomarker genes in the brain: Role of Nrf2/Keap1

“…Therefore it may be assumed that Nrf2 signaling pathway may be connected with MAP Kinase pathway through p38. This observation corroborates the recent finding that Nrf2 was directly influenced by p38 and ROS (Lin et al, 2014).…”

Macrophage Migration Inhibitory Factor: A Novel Inhibitor of Apoptosis Signal-Regulating Kinase 1–p38–Xanthine Oxidoreductase–Dependent Cigarette Smoke–Induced Apoptosis

“…therapeutic target for COPD due to its regulation of p38 (31,59) and possible involvement in bronchitis-related cell turnover, as determined in studies with bronchiolar cell lines (60). To assess the role of ASK1 in CS-induced p38 activation and apoptosis, we used a loss-of-function approach.…”

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

“…Lin et al. () showed that CSE‐induced apoptosis in BEAS‐2B cells was regulated by the ASK‐1/p38 signalling cascade. Another study on BEAS‐2B cells showed that CSE‐induced upregulation of inflammatory cytokines was dependent on the ERK/p38 signalling pathway (Li D et al., ).…”

“…Furthermore, an increased level of activated p38 was observed in pulmonary fibroblasts exposed to CSE (Kim et al, 2011). Lin et al (2014) showed that CSE-induced apoptosis in BEAS-2B cells was regulated by the ASK-1/p38 signalling cascade. Another study on BEAS-2B cells showed that CSE-induced upregulation of inflammatory cytokines was dependent on the ERK/p38 signalling pathway (Li D et al, 2016).…”