Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/62219
Title: Inhibition of caspase-9 aggravates acute liver injury through suppression of cytoprotective autophagy
Authors: Guo, R
Lin, B 
Pan, JF
Liong, EC
Xu, AM
Youdim, M
Fung, ML
So, KF
Tipoe, GL
Issue Date: 2016
Publisher: Nature Publishing Group
Source: Scientific reports, 2016, v. 6 , 32447 How to cite?
Journal: Scientific reports 
Abstract: Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4 -induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy. CCl4 was used as an acute liver injury inducer which caused oxidative stress and apoptosis through up-regulation of HIF-1α, as well as triggered hepatic inflammation and necroptosis via TLR4/NF-κ B pathway. Caspase-9 Thr125 site was firstly phosphorylated by ERK1/2 which subsequently activated the cytoprotective autophagy process to attenuate acute CCl4 injury. Caspase-9 inhibition further aggravated hepatic necroptosis through NF-κ B expression, leading to increased pro-inflammatory mediators levels, suggesting a protective role of caspase-9-dependent autophagy in the inflammatory process as well as its possibility being a new therapeutic target for the treatment of acute liver injury.
URI: http://hdl.handle.net/10397/62219
EISSN: 2045-2322
DOI: 10.1038/srep32447
Appears in Collections:Journal/Magazine Article

Access
View full-text via PolyU eLinks SFX Query
Show full item record

SCOPUSTM   
Citations

2
Last Week
0
Last month
Citations as of Nov 18, 2017

WEB OF SCIENCETM
Citations

1
Last Week
0
Last month
Citations as of Nov 15, 2017

Page view(s)

50
Last Week
1
Last month
Checked on Nov 12, 2017

Google ScholarTM

Check

Altmetric



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.