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The impaired redox balance in peroxisomes of catalase knockout mice accelerates nonalcoholic fatty liver disease through endoplasmic reticulum stress

Title
The impaired redox balance in peroxisomes of catalase knockout mice accelerates nonalcoholic fatty liver disease through endoplasmic reticulum stress
Authors
Hwang, InahUddin, Md JamalPak, Eun SeonKang, HyejiJin, Eun-JungJo, SuinKang, DongminLee, HyukjinHa, Hunjoo
Ewha Authors
하헌주강동민
SCOPUS Author ID
하헌주scopus; 강동민scopus
Issue Date
2020
Journal Title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN
0891-5849JCR Link

1873-4596JCR Link
Citation
FREE RADICAL BIOLOGY AND MEDICINE vol. 148, pp. 22 - 32
Keywords
CatalaseER stressHepatocytesNonalcoholic steatohepatitisPeroxisomal biogenesisPrimary cell culturesReactive oxygen species
Publisher
ELSEVIER SCIENCE INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Peroxisomes are essential organelles for maintaining the homeostasis of lipids and reactive oxygen species (ROS). While oxidative stress-induced endoplasmic reticulum (ER) stress plays an important role in nonalcoholic fatty liver disease (NAFLD), the role of peroxisomes in ROS-mediated ER stress in the development of NAFLD remains elusive. We investigated whether an impaired peroxisomal redox state accelerates NAFLD by activating ER stress by inhibiting catalase, an antioxidant expressed exclusively in peroxisomes. Wild-type (WT) and catalase knockout (CKO) mice were fed either a normal diet or a high-fat diet (HFD) for 11 weeks. HFD-induced phenotype changes and liver injury accompanied by ER stress and peroxisomal dysfunction were accelerated in CKO mice compared to WT mice. Interestingly, these changes were also significantly increased in CKO mice fed a normal diet. Inhibition of catalase by 3-aminotriazole in hepatocytes resulted in the following effects: (i) increased peroxisomal H2O2 levels as measured by a peroxisome-targeted H2O2 probe (HyPer-P); (ii) elevated intracellular ROS; (iii) decreased peroxisomal biogenesis; (iv) activated ER stress; (v) induced lipogenic genes and neutral lipid accumulation; and (vi) suppressed insulin signaling cascade associated with JNK activation. N-acetylcysteine or 4-phenylbutyric acid effectively prevented those alterations. These results suggest that a redox imbalance in peroxisomes perturbs cellular metabolism through the activation of ER stress in the liver.
DOI
10.1016/j.freeradbiomed.2019.12.025
Appears in Collections:
약학대학 > 약학과 > Journal papers
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