Modulation of autophagy in the protective effect of resveratrol on PM2.5‐induced pulmonary oxidative injury in mice

Abstract

Ambient fine particulate matter (PM2.5) is capable of inducing pulmonary oxidative injury. Autophagy maintains basal cellular homeostasis and plays a critical role in the pathogenesis of lung diseases. Resveratrol, a natural polyphenol, is an effective antioxidant agent against particulate matter (PM)-induced injuries. The current study was designed to investigate whether resveratrol can regulate autophagy in the process of PM2.5-mediated pulmonary oxidative injury. In the mice model of PM2.5 exposure, we found that PM2.5 increased the contents of malondialdehyde (MDA) and nitric oxide (NO) while decreased the expression of nuclear factor erythroid-2-related factor 2 in the lungs. The levels of 8-hydroxydeoxyguanosine and inflammatory cytokines were increased following PM2.5 exposure. Histological analysis of the lungs revealed inflammatory change in PM2.5 group. Meanwhile, PM2.5 triggered autophagy, as evidenced by the elevated expression of microtubule-associated proteins light chain 3II, Beclin1 and p62. Transmission electron microscopy images showed that autophagosomes accumulated in the lungs after PM2.5 exposure. Furthermore, resveratrol intervention suppressed autophagy and attenuated the oxidative injury resulting from PM2.5 exposure. Our findings provided a valuable insight into the underlying mechanism for the protective effects of resveratrol against PM2.5-induced lung injury, which involves suppression of the autophagic process. KEYWORDS autophagy, lung, oxidative injury, PM2.5, resveratrol * Yuan Li and Suming Fu contributed equally to this work.

Pathogenic Mechanisms of Secondary Organic Aerosols

“…Other potential SOA-mediated mechanisms could be envisioned if we reason that SOA are part of PM. It has been demonstrated that PM, especially PM2.5, have the capacity to reduce cell proliferation , through cell cycle arrest in different types of cells. ,,,− PM are also known to induce apoptosis and autophagy. ,− Interestingly, a crosstalk between the latter has been documented, , and both can be explained by PM2.5 implication concerning a decrease of mRNA and protein level of mammalian target of rapamycin (mTOR). − Quite relevant, PM2.5-induced apoptosis was found to be mediated by an increase of known apoptotic factors like p53 and a decrease of its inhibitor, SGK1 usually activated by mTOR, resulting in a cascade of different steps and involving a series of molecules such as Bax, cytochrome c , APAF-1, and caspases (Figure ). − Of course, additional studies are required in order to determine the relevance of these speculations.…”

Particulate Matter-Induced Aryl Hydrocarbon Receptor Regulates Autophagy in Keratinocytes

“…In vascular endothelial cells, autophagy-induced by PM 2.5 decreases cell cytotoxicity (Zhou et al ., 2018). In addition, compounds such as resveratrol protect lung cells from PM-induced oxidative injury by inducing autophagy (Li et al ., 2018). However, to date, there have been no studies on the relationship between PM-induced autophagy and AhR activation.…”

Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats

“…Resveratrol is a natural plant antitoxin that can protect against fungal infections, and is also an active ingredient in some herbs that possess capacity to treat inflammation, lipid metabolism, and heart disease [4,5]. Additionally, resveratrol is also documented to have antioxidant, anti-inflammatory, and anti-tumor activities [6–8]. More importantly, resveratrol has been reported to protect against muscle injury [9–12].…”