KEAP the balance between life and death

Cazanave, Sophie C.; Sanyal, Arun J.

doi:10.4161/23723548.2014.968065

Cited by 6 publications

(5 citation statements)

References 10 publications

(15 reference statements)

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“…Increasing UCP2 expression in hepatoma cells may contribute to cell autophagy and may inhibit apoptosis as result of fatty acid injury[ 84 ]. Cellular degradation of Kelch-like ECH-associated protein 1 through the progress of sequestrosome (SQSTM)1/p62-dependent autophagy activates JNK, upregulates expression of Bim and PUMA, and contributes to hepatocyte apoptosis induced by saturated FFAs[ 85 ]. Parkin-mediated mitophagy may mitigate hepatocyte apoptosis, improve mitochondrial quality, and suppress steatosis (lipid accumulation) in animal models of alcoholic fatty liver disease[ 86 ].…”

Section: Autophagymentioning

confidence: 99%

Apoptosis and non-alcoholic fatty liver diseases

Kanda

Matsuoka

Yamazaki

et al. 2018

WJG

210

145

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The number of patients with nonalcoholic fatty liver diseases (NAFLD) including nonalcoholic steatohepatitis (NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma (HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice.

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Section: Autophagymentioning

confidence: 99%

Apoptosis and non-alcoholic fatty liver diseases

Kanda

Matsuoka

Yamazaki

et al. 2018

WJG

210

145

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show abstract

“…Nrf2 is a key transcription factor that induces the expression of antioxidant factors regulated by ARE [ 40 ]. Under unstressed conditions, Keap1, a negative feedback regulator of Nrf2, binds to Nrf2 and accumulates in the cytoplasm as an inactive complex [ 41 ]. This quenching interaction inhibited the expression of Nrf2 and its regulated genes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Carbohydrate Levels on Growth Performance, Body Composition, Antioxidant Capacity, Immunity, and Liver Morphology in Oncorhynchus mykiss under Cage Culture with Flowing Freshwater

Zhao

Wei

Wang

et al. 2022

Aquaculture Nutrition

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The purpose of this study is to investigate the effects of dietary carbohydrate levels on growth performance, body composition, antioxidant capacity, immunity, and liver morphology in Oncorhynchus mykiss under cage culture with flowing freshwater. Fish (initial body weight 25.70 ± 0.24 g) were fed five isonitrogenous (420 g/kg protein) and isolipidic (150 g/kg lipid) diets containing 50.6, 102.1, 151.3, 200.9 and 251.8 g/kg carbohydrate levels, respectively. The results indicated that fish fed diets containing 50.6-200.9 g/kg carbohydrate showed significantly higher growth performance, feed utilization, and feed intake than those fed 251.8 g/kg dietary carbohydrate levels. Based on the analysis of the quadratic regression equation for weight gain rate, the appropriate dietary carbohydrate requirement of O. mykiss was estimated to be 126.2 g/kg. 251.8 g/kg carbohydrate level activated Nrf2-ARE signaling pathway, suppressed superoxide dismutase activity and total antioxidant capacity, and increased MDA content in the liver. Besides, fish fed a diet containing 251.8 g/kg carbohydrate showed a certain degree of hepatic sinus congestion and dilatation in the liver. Dietary 251.8 g/kg carbohydrate upregulated the mRNA transcription level of proinflammatory cytokines and downregulated the mRNA transcription level of lysozyme and complement 3. Whole-body compositions were not affected by dietary carbohydrate levels. In conclusion, 251.8 g/kg carbohydrate level suppressed the growth performance, antioxidant capacity and innate immunity, resulting in liver injury and inflammatory response of O. mykiss. A diet containing more than 200.9 g/kg carbohydrate is not efficiently utilized by O. mykiss under cage culture with flowing freshwater.

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“…Nrf2 regulates its protein level through an autoregulatory loop activating the expression of Keap1, CUL3 and RBX1 [ 33 ]. Keap1 decreases apoptosis and inflammation by reduction of NF-κB activation through Keap1E3 ligase-mediated degradation of IKKβ [ 6 , 20 ]. The increased nuclear accumulation of Nrf2 is caused by down-regulated Jak2/Fyn myocardial signaling inhibiting export of Nrf2 from the nucleus (pathway depicted in the schematic (Fig.…”

Section: Discussionmentioning

confidence: 99%

Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress

et al. 2018

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Fibrosis is a hallmark of maladaptive cardiac remodelling. Here we report that genome-wide quantitative trait locus (QTL) analyses in recombinant inbred mouse lines of C57BL/6 J and DBA2/J strains identified Raf Kinase Inhibitor Protein (RKIP) as genetic marker of fibrosis progression. C57BL/6 N-RKIP−/− mice demonstrated diminished fibrosis induced by transverse aortic constriction (TAC) or CCl4 (carbon tetrachloride) treatment compared with wild-type controls. TAC-induced expression of collagen Iα2 mRNA, Ki67+ fibroblasts and marker of oxidative stress 8-hydroxyguanosine (8-dOHG)+ fibroblasts as well as the number of fibrocytes in the peripheral blood and bone marrow were markedly reduced in C57BL/6 N-RKIP−/− mice. RKIP-deficient cardiac fibroblasts demonstrated decreased migration and fibronectin production. This was accompanied by a two-fold increase of the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2), the main transcriptional activator of antioxidative proteins, and reduced expression of its inactivators. To test the importance of oxidative stress for this signaling, C57BL/6 J mice were studied. C57BL/6 J, but not the C57BL/6 N-strain, is protected from TAC-induced oxidative stress due to mutation of the nicotinamide nucleotide transhydrogenase gene (Nnt). After TAC surgery, the hearts of Nnt-deficient C57BL/6 J-RKIP−/− mice revealed diminished oxidative stress, increased left ventricular (LV) fibrosis and collagen Iα2 as well as enhanced basal nuclear expression of Nrf2. In human LV myocardium from both non-failing and failing hearts, RKIP-protein correlated negatively with the nuclear accumulation of Nrf2. In summary, under conditions of Nnt-dependent enhanced myocardial oxidative stress induced by TAC, RKIP plays a maladaptive role for fibrotic myocardial remodeling by suppressing the Nrf2-related beneficial effects.Electronic supplementary materialThe online version of this article (10.1007/s00395-018-0700-3) contains supplementary material, which is available to authorized users.

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KEAP the balance between life and death

Cited by 6 publications

References 10 publications

Apoptosis and non-alcoholic fatty liver diseases

Apoptosis and non-alcoholic fatty liver diseases

Effects of Dietary Carbohydrate Levels on Growth Performance, Body Composition, Antioxidant Capacity, Immunity, and Liver Morphology in Oncorhynchus mykiss under Cage Culture with Flowing Freshwater

Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress

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