Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice

Nanoplastics-induced developmental and reproductive toxicity,neurotoxicity and immunotoxicity are a focus of widespread attention.However,the effects of nanoplastics(NPs)on glycolipid metabolism and the precise underlying mechanisms are unclear at present.Here,we showed that oral administration of polystyrene nanoparticles(PS-NPs)disrupts glycolipid metabolism,with reactive oxygen species(ROS)identified as a potential key signaling molecule.After PS-NPs treatment,excessive production of ROS induced the infammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2.The activation of nuclear factor-κB(NFκB)signaling pathway induced the phosphorylation of the mitogen-activated protein kinases(MAPK)signaling pathway,which induced the activation of extracellular regulated kinases(ERK)and p38.Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1,in turn,leading to decreased protein kinase B(Akt)activity,which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance.In parallel,phosphorylation of Akt led to loss of control of Fo XO1,a key gene of gluconeogenesis,activating transcription of glucose-6-phosphatase(G6PC)and phosphoenolpyruvate carboxykinase(PEPCK)in a manner dependent on PGC1α.Moreover,the activated ERK promoted lipid accumulation through ERK-PPARγcascades.Therefore,sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes,ACC-1,were up-regulated.Upon treatment with the antioxidant resveratrol,PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice.Based on above,PS-NPs exposure disrupts glycolipid metabolism in mice,with ROS identified as a potential key signaling molecule.

Acetylproteomics analyses reveal critical features of lysine-ε-acetylation in Arabidopsis and a role of 14-3-3 protein acetylation in alkaline response

Lysine-ε-acetylation(Kac)is a post-translational modification(PTM)that is critical for metabolic regulation and cell signaling in mammals.However,its prevalence and importance in plants remain to be determined.Employing high-resolution tandem mass spectrometry,we analyzed protein lysine acetylation in five representative Arabidopsis organs with 2~3 biological replicates per organ.A total of 2887 Kac proteins and 5929 Kac sites were identified.This comprehensive catalog allows us to analyze proteome-wide features of lysine acetylation.We found that Kac proteins tend to be more uniformly expressed in different organs,and the acetylation status exhibits little correlation with the gene expression level,indicating that acetylation is unlikely caused by stochastic processes.Kac preferentially targets evolutionarily conserved proteins and lysine residues,but only a small percentage of Kac proteins are orthologous between rat and Arabidopsis.A large portion of Kac proteins overlap with proteins modified by other PTMs including ubiquitination,SUMOylation and phosphorylation.Although acetylation,ubiquitination and SUMOylation all modify lysine residues,our analyses show that they rarely target the same sites.In addition,we found that“reader”proteins for acetylation and phosphorylation,i.e.,bromodomain-containing proteins and GRF(General Regulatory Factor)/14-3-3 proteins,are intensively modified by the two PTMs,suggesting that they are main crosstalk nodes between acetylation and phosphorylation signaling.Analyses of GRF6/14-3-3λreveal that the Kac level of GRF6 is decreased under alkaline stress,suggesting that acetylation represses plant alkaline response.Indeed,K56ac of GRF6 inhibits its binding to and subsequent activation of the plasma membrane H+-ATPase AHA2,leading to hypersensitivity to alkaline stress.These results provide valuable resources for protein acetylation studies in plants and reveal that protein acetylation suppresses phosphorylation output by acetylating GRF/14-3-3 proteins.