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DNase II activated by the mitochondrial apoptotic pathway regulates RIP1-dependent non-apoptotic hepatocyte death via the TLR9/IFN-β signaling pathway by Yoshinobu Saito; Hayato Hikita; Yasutoshi Nozaki; Yugo Kai; Yuki Makino; Tasuku Nakabori; Satoshi Tanaka; Ryoko Yamada; Minoru Shigekawa; Takahiro Kodama; Ryotaro Sakamori; Tomohide Tatsumi; Tetsuo Takehara is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is DNase II activated by the mitochondrial apoptotic pathway regulates RIP1-dependent non-apoptotic hepatocyte death via the TLR9/IFN-β signaling pathway about?

Cell death, including apoptotic and non-apoptotic cell death, is frequently observed in liver disease. Upon activation of the mitochondrial apoptotic pathway, mitochondria release not only apoptogenic cytochrome c but also mitochondrial DNA (mtDNA) into the cytosol. The impact of DNase II, a lysosomal acid DNase that degrades mtDNA, on hepatocyte death remains unclear. Administration of ABT-737, a Bcl-xL inhibitor, upregulated DNase II activity in murine hepatocyte cell line BNL CL.2 cells and induced apoptosis. In cells treated with DNase II siRNA, ABT-737 led to accumulation of mtDNA in the cytosol and increased expression of interferon (IFN)-β and induction of propidium iodide (PI)-positive cells, in addition to apoptosis. Induced PI-positive cells were suppressed by RIP1 inhibitor, Necrostatin-1, but not by pan-caspase inhibitor, ZVAD-FMK, suggesting non-apoptotic cell death. Both the increase in IFN-β and the induction of non-apoptotic cell death were abolished by administering a TLR9 antagonist, ODN2088, or by the removal of mtDNA from cells with ethidium bromide. Hepatocyte-specific Mcl-1 knockout mice developed hepatocyte apoptosis accompanied by upregulated DNase II activi

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Author

Yoshinobu Saito; Hayato Hikita; Yasutoshi Nozaki; Yugo Kai; Yuki Makino; Tasuku Nakabori; Satoshi Tanaka; Ryoko Yamada; Minoru Shigekawa; Takahiro Kodama; Ryotaro Sakamori; Tomohide Tatsumi; Tetsuo Takehara

Publisher

Nature Publishing Group; Springer Science and Business Media LLC (ISSN 1350-9047)

Published

2018

Language

EN

ISBN

9784141801801

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)