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Liu, j.

Publications and source records attributed to Liu, j..

2 recordsLinked to original sources

Exposure to titanium dioxide nanoparticles accelerates abnormal fat deposition through the mediation of the ROS via the AGE-RAGE signaling pathway in mice

Titanium dioxide nanoparticles (TiO2 NPs) are widely added to various types of foods as food additives. Previous studies have shown that TiO2 NPs exposure can cause abnormal deposition of adipose tissue in organisms, resulting in lipid metabolism disorder. However, the potential molecular mechanisms underlying TiO2 NPs effects have yet to be elucidated. In this study, our data indicated that TiO2 NPs (100 mg/Kg BW, 20 nm) accelerated abnormal fat deposition in the epididymal adipose tissues and disturbed the level of blood glucose subsequently in normal-fat diet mice. Further studies showed that TiO2 NPs at a concentration of 100 {micro}g/mL significantly induced the proliferation and differentiation of 3T3-L1 preadipocytes. Mechanistic studies we revealed that TiO2 NPs induced the overproduction of reactive oxygen species (ROS) in the cytoplasm, which subsequently upregulated the expression of receptors for advanced glycation end products (AGEs) leading to lipid accumulation in the adipocytes with a higher level of ROS. However, the antioxidant N-acetylcysteine (NAC) was a therapeutic potential for lipid overaccumulation in the adipocytes. This study provides insight into the mechanism underlying fat deposition induced by TiO2 NPs and highlighted the need for reevaluation of food-grade TiO2 NPs exposure in daily life.

cell biology↗

Cryo-EM structures of inactive and Gi-coupled GABAB heterodimer

Metabotropic GABAB G protein-coupled receptor functions as a mandatory heterodimer of GB1 and GB2 subunits and mediates inhibitory neurotransmission in the central nervous system. Each subunit is composed of the extracellular Venus flytrap (VFT) domain and transmembrane (TM) domain. Here we present cryo-EM structures of human full-length heterodimeric GABAB receptor in the antagonist-bound inactive state and in the active state complexed with agonist and positive allosteric modulator in the presence of Gi1 protein at a resolution range of 2.8-3.0 [A]. Cryo-EM analysis of the activated-GABAB-Gi1 complex revealed that Gi1 couples to the activated receptor primarily in three major conformations, one via GB1 TM and two via GB2 TM, respectively. Our structures reveal that agonist binding stabilizes the closure of GB1 VFT, which in turn triggers a rearrangement of TM interfaces between two subunits from TM3-TM5/TM3-TM5 in the inactive state to TM6/TM6 in the active state and finally induces the opening of intracellular loop 3 and synergistically shifting of TM3, 4 and 5 helices in GB2 TM domain to accommodate the 5-helix of Gi1. These results provide a structural framework for understanding class C GPCR activation and a rational template for allosteric modulator design targeting dimeric interface of GABAB receptor.

molecular biology↗