Fine Particulate Matter Leads to Unfolded Protein Response and Shortened Lifespan by Inducing Oxidative Stress in C. elegans

Abstract

Oxidative stress has been proven as one of the most critical regulatory mechanisms involved in fine Particulate Matter- (PM2.5-) mediated toxicity. For a better understanding of the underlying mechanisms that enable oxidative stress to participate in PM2.5-induced toxic effects, the current study explored the effects of oxidative stress induced by PM2.5 on UPR and lifespan in C. elegans. The results implicated that PM2.5 exposure induced oxidative stress response, enhanced metabolic enzyme activity, activated UPR, and shortened the lifespan of C. elegans. Antioxidant N-acetylcysteine (NAC) could suppress the UPR through reducing the oxidative stress; both the antioxidant NAC and UPR inhibitor 4-phenylbutyric acid (4-PBA) could rescue the lifespan attenuation caused by PM2.5, indicating that the antioxidant and moderate proteostasis contribute to the homeostasis and adaptation to oxidative stress induced by PM2.5.

Toxic Assessment of Heavily Traffic-related Fine Particulate Matter Using an in-vivo Wild-type Caenorhabditis elegans Model

“…6(a)). The trend of survival rate data in the present study is in agreement with those of previous studies which linked PM 2.5 concentration with the decreasing population of exposed nematodes (Zhao et al, 2014;Sun et al, 2015Sun et al, , 2016Chung et al, 2019;Zhao et al, 2019). Sun et al (2015) also reported that acute exposure of C. elegans to coal combustion related-PM 2.5 at 100 mg L -1 significantly decreased the population of the exposed nematodes.…”

“…The results were similar to that of one our previous report (Chung et al, 2019), revealing that the highest concentrations of ambient PM 2.5 from rural areas (Chung et al, 2019) and the PM 2.5 with various concentrations in the present study significantly accelerated the ageing of the nematodes to have lifespans shorter than their typical ones. Zhao et al (2019) indicated that ambient PM 2.5 on a college campus at the concentrations of 10 and 100 mg L -1 caused the oxidative stress activation, increased metabolic enzyme response, induced unfold protein response (UPR), and decreased the lifespan of the nematodes. Furthermore, the antioxidant, such as N-acetylcysteine, could be treated in C. elagans to suppress the oxidative stress from UPR and then to recovery the lifespan attenuation induced by fine particulate (Zhao et al, 2019).…”

“…Zhao et al (2019) indicated that ambient PM 2.5 on a college campus at the concentrations of 10 and 100 mg L -1 caused the oxidative stress activation, increased metabolic enzyme response, induced unfold protein response (UPR), and decreased the lifespan of the nematodes. Furthermore, the antioxidant, such as N-acetylcysteine, could be treated in C. elagans to suppress the oxidative stress from UPR and then to recovery the lifespan attenuation induced by fine particulate (Zhao et al, 2019).…”

“…The 1 mm long free-living soil nematode used in the animal model Caenorhabditis elegans (C. elegans) established by Sydney Brenner in 1965 plays a key role in the decomposition and nutrient cycling (Sohlenius, 1980). The C. elegans in-vivo system has been used as a model for the assessment of toxic effects of air pollutants (Zhao et al, 2014;Sun et al, 2015Sun et al, , 2016Yang et al, 2016;Wu et al, 2017;Wang et al, 2018;Chung et al, 2019;Zhao et al, 2019) because it shows much advantages over other animal models: production of large number of progeny (100-200 from a single hermaphrodite), transparency, rapid life cycle (3 days), short lifespan (2-3 weeks), low cost, and easy laboratory cultivation (Brenner, 1974;Nass and Hamza, 2007). Moreover, C. elegans follows the widely accepted ethical principles, known as Three Rs (Reduction of the use of higher animals, Refinement of current techniques, and Replacement of animals with alternative methods) (Brenner, 1974).…”

“…For the studies of PM 2.5 toxicity in C. elegans, oxidative stress seems to be one of the primary contributing factors to PM 2.5 -mediated toxicity. Oxidative stress was induced via the mir-231-SMK-1-SOD-3/SOD-4/CTL-3 signaling pathway after exposure of C. elegans to coal combustion-related PM 2.5 (Wu et al, 2017) and the expression levels of certain antioxidant enzymes such as glutathione S-transferase (GST-4), superoxide dismutase (SOD-3), glutathione peroxidase (GSH-Px), and catalase (CAT) increased in response to the oxidative stress (Zhao et al, 2019). Currently, few studies focused on the toxic effects of TRAP PM 2.5 on C. elegans models: therefore, this study aims to evaluate the toxicity responses of TRAP PM 2.5 between 24 March and 15 April in 2018 in a major road in Taichung City, Taiwan.…”