Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway
العنوان: | Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway |
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المؤلفون: | Tianming Qiu, Xiance Sun, Rushan Yan, Zhidong Wang, Sen Wei, Guang Yang, Ni Gao, Liping Jiang, Xiaofang Liu, Jie Bai, Pei Pei, Shuangyue Qi, Xiaofeng Yao, Lei Yang |
المصدر: | Cell Death and Disease, Vol 9, Iss 10, Pp 1-16 (2018) |
بيانات النشر: | Nature Publishing Group, 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Programmed cell death, Cell Survival, Taurine, Immunology, Inflammation, Real-Time Polymerase Chain Reaction, Arsenic, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Microscopy, Electron, Transmission, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, Autophagy, Pyroptosis, medicine, Animals, Humans, Arsenic trioxide, lcsh:QH573-671, Arsenic toxicity, integumentary system, lcsh:Cytology, Inflammasome, Hep G2 Cells, Cell Biology, medicine.disease, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, medicine.symptom, Signal Transduction, medicine.drug |
الوصف: | Arsenic exposure causes nonalcoholic steatohepatitis (NASH). Inflammation is a key contributor to the pathology of nonalcoholic fatty liver disease (NAFLD), including NASH. However, it is unclear how arsenic induces inflammation. In mouse livers, we show that arsenic trioxide (As2O3) induced NASH, increased autophagy and NLRP3 inflammasome activation, increased lipid accumulation, and resulted in dysregulation of lipid-related genes. Supplemented with taurine (Tau) attenuated the inflammation and autophagy caused by As2O3. In HepG2 cells, we found that As2O3-induced pyroptotic cell death was dependent upon the activation of NLRP3 inflammasome, which was CTSB-dependent. In addition, inhibiting autophagy alleviated the As2O3-induced increase of cytosolic CTSB expression and subsequent release of LDH, activation of the NLRP3 inflammasome, and pyroptosis. Moreover, we found that Tau alleviated As2O3-induced elevation of autophagy, CTSB expression, and activation of the NLRP3 inflammasome, and reduced the release of LDH, pyroptotic cell death, and inflammation. Interestingly, As2O3-induced lipid accumulation could not be alleviated by either inhibition of autophagy nor by inhibition of CTSB. Additionally, neither inhibition of the NLRP3 inflammasome or Tau treatment could alleviate lipid accumulation. These results demonstrated that As2O3-induced pyroptosis involves autophagy, CTSB, and the NLRP3 inflammasome cascade, and that Tau alleviates As2O3-induced liver inflammation by inhibiting the autophagic-CTSB-NLRP3 inflammasomal pathway rather than decreasing lipid accumulation. These findings give insight into the association of autophagy, inflammation, pyroptosis, and NASH induced by As2O3. |
اللغة: | English |
تدمد: | 2041-4889 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35d25f4c13dce5ef8942ce371d4fcc7dTest http://link.springer.com/article/10.1038/s41419-018-1004-0Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....35d25f4c13dce5ef8942ce371d4fcc7d |
قاعدة البيانات: | OpenAIRE |