Publication: Histone deacetylase 6 inhibitor ACY1215 ameliorates mitochondrial dynamic and function injury in hepatocytes by activating AMPK signaling pathway in acute liver failure mice
Authors
Chen, Qian ; Wang, Yao ; Jiao, Fangzhou ; Shi, Chunxia ; Pei, Maohua ; Wang, Luwen ; Gong, Zuojiong
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-237
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info:eu-repo/semantics/article
Description
Abstract
Acute liver failure (ALF) is often
accompanied by dynamic and functional disorders of
mitochondria in hepatocytes. The histone deacetylase 6
inhibitor Rocilinostat (ACY1215) has a hepatoprotective
effect. However, its protective effect on mitochondria of
hepatocytes and its related mechanisms in ALF remain
unknown. The purpose of the present study was to
elucidate the protective effect of ACY1215 on
mitochondrial of hepatocytes in ALF by regulating
AMPK signaling pathway. LPS and D-Gal were used to
induce ALF model in C57BL/6 mice. D-Gal and TNF-α
were applied in L02 cells as model group. ACY1215
was administered to the mice or culture cells before the
model' s establishment as ACY1215 group. The normal
group in mice and L02 cells was not given any drug
intervention. ACY1215 improves liver histological and
functional changes in ALF model mice. Compared with
normal group, the expression of p-AMPK and p-ACC
proteins was decreased in model group. ACY1215
activated the AMPK signaling pathway with an increase
of p-AMPK and p-ACC proteins level in model group.
ACY1215 treatment decreased levels of mitochondrial
fission proteins DRP1 and FIS1, and enhanced levels of
mitochondrial fusion proteins MFN1, MFN2 and OPA1
in models. MtDNA copies in model group was decreased
compared with normal group, but ACY1215 elevated the
mtDNA copies in models. Mitochondrial respiratory
electron transfer chain Complex I-III and citrate
synthase (CS) activities in model group were decreased
compared with normal group, but ACY1215 treatment
enhanced these activities in model group. ACY1215
protects against dynamic disorders and dysfunction of
mitochondria in hepatocytes in ALF by activating
AMPK signaling pathway.
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Citation
Histology and Histopathology Vol. 35, nº9 (2020)
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