›› 2019, Vol. 39 ›› Issue (8): 812-.doi: 10.3969/j.issn.1674-8115.2019.08.002

• Original article (Basic research) • Previous Articles     Next Articles

SIRT7 protecting hepatocytes LPS or D-GalN/LPS-induced apoptosisattenuating endoplasmic reticulum stress via inactivation of GRP78

RUAN Xin1, ZHANG Ying-ting1, HAN Ke-qi1, LIN Long-shuai2, CHEN Chen1, YUE Ming1, WANG Chu-qiao1, SUN Ying-gang3, ZHAO Qing-hua2, HE Ming1   

  1. 1. Department of Pathophysiology, Shanghai Jiao Tong University College of Basic Medical Sciences; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai 200025, China; 2. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 201620, China; 3. Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
  • Online:2019-08-28 Published:2019-09-23
  • Supported by:
    National Natural Science Foundation of China,81470841;Shanghai Pujiang Program,16PJ1405400,16PJ0004679;Natural Science Foundation of Shanghai,19ZR1428400;Medicine and Industry Crossing Project Shanghai Jiao Tong University,YG2017MS02

Abstract: Objective · To investigate the effects of SIRT7 on acute liver injury inducedlipopolysaccharide (LPS) or D-galactosamine (D-GalN)/LPS and its mechanisms. Methods · Thirteen-week-old C57BL/6J mice were randomly divided into normal saline group (n5), LPS group (n7), and D-GalN/ LPS group (n8), which were respectively intraperitoneally injected with normal saline, LPS or D-GalN/LPS. The serum and livers of normal saline group and LPS group mice were collected 24 hours after the injection, and the samples of D-GalN/LPS group were collected 8 hours after the injection. Liver pathological changes were comparedusing H-E staining, and serological indicators of the mice three groups were also compared. Liver apoptosis and inflammatory cells infiltration were determinedTUNEL staining and F4/80 staining. Meanwhile, the mRNA levels of SIRT7 and inflammatory factors, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) in livers were detectedrealtime-PCR. Western blotting was used to detect the protein levels of SIRT7, cleaved-caspase3 and the 78 kDa glucose regulated protein (GRP78) in moliver tissues. AML-12 cell line overexpressing SIRT7 was stimulated with LPS, and Western blotting was used to study the roles of SIRT7 in the endoplasmic reticulum (ER) stress inducedLPS in vitro. Results · LPS orD-GalN/LPSinduced inflammatorycellsinfiltration,hyperemia and hepatocytesapoptosis inlivers.Meanwhile, serum glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) in the mice treatedLPS or D-GalN/LPS were significantly increased. Moreover, both liver SIRT7 mRNA and protein levels were down-regulated, while GRP78 protein in ER stress pathway was up-regulated. In AML-12 cells, SIRT7 over inhibited LPS-induced up-regulation of GRP78. Conclusion · SIRT7 protects against LPS or D-GalN/LPS-induced hepatocytes apoptosisattenuating ER stress via inactivating GRP78.

Key words: sirtuin, sepsis, SIRT7, acute liver injury, endoplasmic reticulum stress, apoptosis

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