[S100 calcium binding protein A16 promotes fat synthesis through endoplasmic reticulum stress in HepG2 cells].

Abstract

The aim of this study was to investigate the role of S100 calcium binding protein A16 (S100A16) in lipid metabolism in hepatocytes and its possible biological mechanism. HepG2 cells (human hepatoma cell line) were cultured with fatty acid to establish fatty acid culture model. The control model was cultured without fatty acid. Each model was divided into three groups and transfected with S100a16 over-expression, shRNA and vector plasmids, respectively. The concentration of triglyceride (TG) in the cells was measured by kit, and the lipid droplets was observed by oil red O staining. Immunoprecipitation and mass spectrometry were used to find the interesting proteins interacting with S100A16, and the interaction was verified by immunoprecipitation. The further mechanism was studied by Western blot and qRT-PCR. The results showed that the intracellular lipid droplet and TG concentrations in the fatty acid culture model were significantly higher than those in the control model. The accumulation of intracellular fat in the S100a16 over-expression group was significantly higher than that in the vector plasmid transfection group. There was an interaction between heat shock protein A5 (HSPA5) and S100A16. Over-expression of S100A16 up-regulated protein expression levels of HSPA5, inositol-requiring enzyme 1α (IRE1α) and pIREα1, which belong to endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway. Meanwhile, over-expression of S100A16 up-regulated the mRNA expression levels of adipose synthesis-related gene Srebp1c, Acc and Fas. In the S100a16 shRNA plasmid transfection group, the above-mentioned protein and mRNA levels were lower than those of vector plasmid transfection group. These results suggest that S100A16 may promote lipid synthesis in HepG2 cells through endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway.

• Authors: Jing-Bao Kan, Ge-Qian Shen, Jie Yang, Pei Tong, Ri-Hua Zhang, Xiu-Bin Liang, Dong-Ming Su, Dong Li, Yun Liu
• Journal: Sheng li xue bao : [Acta physiologica Sinica] (Sheng Li Xue Bao) Vol. 71 Issue 2 Pg. 279-286 (Apr 25 2019) ISSN: 0371-0874 [Print] China
• PMID: 31008487 (Publication Type: Journal Article)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• S100 Proteins
• S100A16 protein, human
• Triglycerides
• X-Box Binding Protein 1
• XBP1 protein, human
• ERN1 protein, human
• Protein Serine-Threonine Kinases
• Endoribonucleases

Topics

• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress
• Endoribonucleases (physiology)
• Heat-Shock Proteins (physiology)
• Hep G2 Cells
• Humans
• Lipid Metabolism
• Protein Serine-Threonine Kinases (physiology)
• S100 Proteins (physiology)
• Triglycerides (biosynthesis)
• X-Box Binding Protein 1 (physiology)