Melatonin enhances autophagy and decreases apoptosis induced by nanosilica in RAW264.7 cells

Abstract

Melatonin is one of the main hormones that regulate biological rhythms and have immunomodulation, anti‐inflammatory, and antioxidation functions. In this study, we aimed to explore the effect of melatonin on the autophagy, apoptosis, and inflammatory reaction of macrophages (RAW264.7 cells) stimulated by nanosilica. SiO2 (100 mg/mL, 10–20 nm) was used to stimulate RAW264.7 cells at different time points (0, 2, 4, 8, 12, and 24 hr). Melatonin (200 μM) was added to SiO2‐stimulated macrophages at 12 hr. Beclin‐1, LC3, Bax, Bcl‐2, and Caspase‐3 were examined with western blotting. Flow cytometry was used to detect apoptosis. The levels of TNF‐α, IL‐1β, and IL‐18 were detected by ELISA. The level of TNF‐α in the supernatant of SiO2‐stimulated cells gradually increased with time but decreased following melatonin administration. In contrast, the expression of IL‐1β and IL‐18 increased after melatonin treatment. LC3 and Bax signaling pathways were activated in SiO2‐stimulated RAW264.7 cells, showing elevated expression of LC3 and reduced expression of Bax in the melatonin‐treated cells. GFP‐LC3 puncta were significantly increased in SiO2‐stimulated RAW264.7 cells and decreased in melatonin‐treated cells. The apoptotic rate in SiO2‐stimulated RAW264.7 cells increased with time and decreased after melatonin treatment, and the number of phagosomes increased with the stimulation of nanosilica and the treatment of melatonin. Melatonin might promote autophagy and inhibit apoptosis as well as inflammatory responses of RAW264.7 cells stimulated by nanosilica. © 2019 IUBMB Life, 2019

A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy

“…Of the different compounds evaluated, the phenanthroimidazole 6 derivative was found to induce autophagy and apoptosis; thus, it could prove to be a novel anti-cancer drug [516]. In nanosilica stimulated RAW264.7 cells, melatonin was found to increase LC3 expression and decrease Bax expression, suggesting that autophagy was promoted, and apoptosis was inhibited [517]. Sasanquasaponin ΙΙΙ obtained from Schima crenata Korth was found to upregulate LC3-II expression in melanoma cells and induce autophagy; hence, it can be used as an anti-cancer drug to treat melanoma [518].…”

Protection of melatonin against long‐term radon exposure‐caused lung injury

“…The protective effect of melatonin, which can defend chromosome damage and oxidative stress induced by environmental toxins has been confirmed by experiments both in vitro and in vivo. In addition, some other studies also showed that melatonin could regulate the autophagy in the protection against oxidative stress 28,29 …”

“…In addition, some other studies also showed that melatonin could regulate the autophagy in the protection against oxidative stress. 28,29 Autophagy is a process to degrade its own organelle and other macromolecules through lysosome, featured by the formation of autophagosome. 30 The stimulation of autophagy could maintain homeostasis and viability of normal cells.…”

Melatonin accelerates the developmental competence and telomere elongation in ovine SCNT embryos

“…In addition, melatonin is produced in some reproductive tissues such as ovaries, uterus, placenta, and testes. Melatonin is considered a multitasking molecule that regulates many cellular functions, including: antioxidant and anti-apoptotic properties [ 27 – 29 ], induction of autophagy [ 30 , 31 ], regulation of epigenetic enzymes [ 5 , 22 ], and telomere length [ 22 , 32 ].…”