Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

Abstract

Background: Heat causes bronchial epithelial cell apoptosis, which is a known factor contributing to airway damage during inhalation injury. Accumulating evidence has shown the effect of curcumin on inhibiting apoptosis. In this study, we investigated whether curcumin suppresses heat-induced apoptosis in bronchial epithelial cells and the underlying mechanism. Methods: Bronchial epithelial cell line 16HBE140 cells were incubated at either 42 °C, 47 °C, 52 °C, or 57 °C for 5 min in a cell incubator and then returned back to normal culture conditions (37 °C). An in vivo thermal inhalation injury rat model was established with a heat gun blowing hot air into the airway of rats. 16HBE140 cells and lung tissue were obtained for further study with or without curcumin treatment. Cell viability was determined by measuring the absorbance of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). 2',7'-dichlorofluorescein diacetate fluorescence was used as a measure of reactive oxygen species (ROS) production. Levels of Bcl2, Bax, α-ATP, cleaved Poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, gp91^phox, p47^phox, p67^phox, p22^phox, p40^phox, and Rac were determined by Western blotting. TUNEL staining was used to determine apoptosis. Results: Heat treatment triggered the apoptosis of 16HBE140 cells as shown by the increase in apoptosis molecular markers, including Bcl-2, Bax, cleaved PARP, and cleaved caspase-3. Administration of curcumin significantly inhibited apoptosis of 16HBE140 cells and suppressed the membrane translocation of NADPH oxidase 2 cytosolic components, as well as ROS production. Downregulation of Akt and mTOR phosphorylation induced by heat was also reversed by curcumin. Furthermore, we demonstrated that NADPH oxidase 2 is upstream of Akt/mTOR in heat-induced apoptosis. The protective role of curcumin on bronchial epithelia apoptosis was also confirmed in vivo by a rat inhalation injury model. Conclusion: This study demonstrates that one of the critical mechanisms underlying curcumin inhibiting heat-induced apoptosis is through suppressing NADPH Oxidase 2 and activating the Akt/mTOR signaling pathway in bronchial epithelial cells.

Dietary curcumin supplementation enhanced growth performance, intestinal digestion, and absorption and amino acid transportation abilities in on‐growing grass carp ( Ctenopharyngodon idella )

“…Unexpectedly, the effects of curcumin on TOR were diverse in different cells or animals. Our study was coincident with the study of curcumin on bronchial epithelial cells of rats (Peng et al., 2017). However, there are inconsistent reports that curcumin has the potential to inhibit TOR signalling in human bladder cancer cells (Tian et al., 2017), human gastric cancer cells (Li et al., 2017), mouse prostate cancer cells (Narayanan, Nargi, Randolph, & Narayanan, 2009) and mouse cardiomyocytes (Yang, Xu, Li, & Jiang, 2013).…”

“…Furthermore, TOR was found to activate S6 kinase 1 (S6K1) and depress eukaryotic initiation factor 4E‐binding protein 1 (4E‐BP1) in mammals (Nissim & Nahum, 2004). A previous study found that curcumin triggered the mTOR signalling pathway in the bronchial epithelial cells of rats (Peng, Pu, Tang, & Wu, 2017). However, no study has explored the relationship among curcumin, AAT, and PepT1, and the TOR signalling pathway, which requires further study.…”

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

“…ROS generation is known to be an important factor in tumor cell death [26, 27]. To further confirm the role of ROS on PD-mediated apoptosis, HeLa and C33A cells were treated with PD to elevate levels of intracellular ROS production (Fig.…”

Dose‐response assessment of chemically modified curcumin in experimental periodontitis

“…However, it is important to consider that these apparently contradictory findings may be related with the final concentration of CMC2.24 in vivo and within the macrophages in vitro. Other in vitro studies report contrasting effects of natural curcumin on production of ROS, depending on the cell type and concentration . In vivo, administration of natural curcumin has been shown to reduce oxidative stress by inhibiting NF‐kB signaling, which would also decrease the expression of various cytokines.…”

“…Other in vitro studies report contrasting effects of natural curcumin on production of ROS, depending on the cell type and concentration. [37][38][39][40][41][42] In vivo, administration of natural curcumin has been shown to reduce oxidative stress by inhibiting NF-kB signaling, 43 which would also decrease the expression of various cytokines. In fact, our research group has recently shown that CMC2.24 inhibits NF-kB signaling.…”