PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and Mitochondrial Dysfunction

Abstract

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood–brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases.

Impact of Micro- and Nanoplastics on Mitochondria

“…MNPs augment neurotoxicity in SHSY-5Y cells through the activation of autophagy and mitochondrial dysfunction, which are modulated by mitochondrial oxidative stress. Hence, mitochondrial damage caused by oxidative stress may be involved in the pathological mechanisms of MNP-evoked neurodegenerative diseases [ 65 ].…”

Autophagy regulation by inorganic, organic, and organic/inorganic hybrid nanoparticles: Organelle damage, regulation factors, and potential pathways

“…[127] PS-NPs have been shown to penetrate the blood-brain barrier. Tang et al [128] found that PS-NPs induced ROS production Abbreviations: Akt, protein kinase B; AMPK, AMP-activated protein kinase; CIR NLP, nanoliposomes; CL, cationic liposomes; CSNPs, chitosan nanoparticles; ERK1/2, Extracellular signal-regulated kinase 1/2; JNK, c-Jun amino(N)-terminal kinase; mTOR, mammalian target of rapamycin; NQ, quercetin nanoparticles; PAMAM, polyamidoamine; PBS, phosphate buffered salin; PS-NPs, polystyrene nanoparticles; ROS, reactive oxygen species; TTF1-NPs, 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone nanoparticle. cannot be ignored.…”

“…[ 127 ] PS‐NPs have been shown to penetrate the blood‐brain barrier. Tang et al [ 128 ] found that PS‐NPs induced ROS production and mitochondrial damage in SHSY‐5Y cells. NPs‐induced mitochondria‐dependent apoptosis and autophagy could potentially trigger neurodegenerative diseases.…”

The Impact of Micro- and Nanoplastics on Aquatic Organisms: Mechanisms of Oxidative Stress and Implications for Human Health—A Review

“…However, exposure to micro-and nanoplastics can disrupt the balance between ROS production and scavenging, leading to ROS overproduction. In addition, micro-and nanoplastics can also lead to the translocation of cytochrome c from mitochondria to the cytoplasm, which can trigger the activation of caspases and the induction of apoptosis [102,103]. The antioxidant defense system plays a critical role in protecting cells against oxidative stress induced by micro-and nanoplastics.…”