Xiangxiang Li,Shaoyang Hu,Zelian Yu,Falin He,Xingchen Zhao,Rutao Liu
Nanoplastics (NPs) are emerging pollutants worldwide. Particularly worrisome is that although studies have reported that NPs can amplify the biotoxicity of environmental pollutants, the specific mechanism remains unclear. Here, we found that NPs, even without significant toxicity (cell survival: 99.11%), amplified the hepatocyte toxicity of Cd2+. Mechanistically, higher Cd2+ uptake (Δ = 23.80%) combined with crucial intracellular desorption behavior of Cd2+ loaded in NPs (desorption rate: 82.70%) were identified as prerequisites for NPs amplifying Cd2+ cytotoxicity. As for toxigenic pathways, the inflammatory response and calcium (Ca) signaling pathway were identified as the primary molecular events leading to the amplification of Cd2+ cytotoxicity. Further phenotypic monitoring revealed that NPs synergized with Cd2+ to induce more severe pyroptosis and apoptosis by activating the inflammatory caspase-1-dependent and Ca2+-mitochondrial-caspase-3 pathways to a greater extent, respectively. This study reveals and proves for the first time the “Trojan horse” effects of NPs, thus elucidating the actual mechanisms by which NPs act as toxicity amplifiers of pollutants, providing significant insights into accurate risk assessment of NPs in composite pollution.
Ritian Jin,Haowei Ren,Minhe Liao,Jiaqi Shang,Dangfeng Wang,Meng Li,Ning Liu
The peptide VLATSGPG (VLA) is known to inhibit dipeptidyl peptidase IV (DPP-IV), although its mechanism in relieving endoplasmic reticulum (ER) stress is unclear. In this study, we found that treating HepG2 cells with 1.0 mM VLA reduced DPP-IV activity by 73.7 ± 4.8% without changing the DPP-IV mRNA expression level. In addition, 1.0 and 0.5 mM VLA alleviated palmitic acid (PA)-induced cell death and intracellular calcium imbalances. The levels of apoptosis-related proteins (caspase-3, caspase-9, and CHOP) were reduced by VLA treatment, which was presumed to be related to ER stress. Further studies confirmed that VLA alleviated PA-induced morphological damage to the ER and reduced the levels of the ER stress marker proteins (BIP, p-PERK, and p-IRE1α). VLA alleviated PA-induced ER stress in HepG2 cells independent of DPP-IV enzymatic activity inhibition. These findings have implications for developing novel treatment approaches for liver diseases caused by ER stress.
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