Ethanol targets nucleoredoxin/dishevelled interactions and stimulates phosphatidylinositol 4-phosphate production in vivo and in vitro

Arellanes‐Robledo, Jaime; Reyes‐Gordillo, Karina; Ibrahim, Joseph; Leckey, Leslie C.; Shah, Ruchi; Lakshman, M

doi:10.1016/j.bcp.2018.08.021

Cited by 14 publications

(21 citation statements)

References 53 publications

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“…This is a widely used model that includes the high‐fat Lieber‐DeCarli diet regime plus single‐binge of ethanol to induce the early stage of ALD 22 . The experimental procedure was performed as previously reported 12 . Briefly, 5% ethanol in liquid diet was administered for 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…It has been shown that NXN negatively regulates WNT/β‐catenin pathway by interacting with dishevelled (DVL), an essential mediator in the Wnt signalling; interestingly, NXN/DVL interaction is dissociated by increased ROS production which enables DVL to activate the downstream WNT/β‐catenin signalling pathway 6 . Recently, we have shown that NXN/DVL interaction ratio is altered by ethanol and as a result, this alteration disrupts DVL‐dependent processes during ALD progression 11,12 . These evidences have suggested that other signalling pathways regulated by NXN might be also altered in ALD.…”

Section: Introductionmentioning

confidence: 98%

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Nucleoredoxin interaction with flightless‐I/actin complex is differentially altered in alcoholic liver disease

Alarcón-Sánchez

Guerrero-Escalera

Rosas-Madrigal

et al. 2020

Basic Clin Pharma Tox

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Alcoholic liver disease (ALD) may be attributed to multiple hits driving several alterations. The aim of this work was to determine whether nucleoredoxin (NXN) interacts with flightless-I (FLII)/actin complex and how this ternary complex is altered during ALD progression induced by different ALD models. ALD was recapitulated in C57BL/6J female mice by the well-known ALD Lieber-DeCarli model, and by an in vitro human co-culture system overexpressing NXN. The effects of ethanol and low doses of lipopolysaccharides (LPS) and diethylnitrosamine (DEN) were also evaluated in vivo as a first approach of an ALD multi-hit protocol. We demonstrated that NXN interacts with FLII/actin complex. This complex was differentially altered in ALD in vivo and in vitro, and NXN overexpression partially reverted this alteration. We also showed that ethanol, LPS and DEN synergistically induced liver structural disarrangement, steatosis and inflammatory infiltration accompanied by increased levels of proliferation (Ki67), ethanol metabolism (CYP2E1), hepatocarcinogenesis (GSTP1) and LPS-inducible (MYD88 and TLR4) markers. In summary, we provide evidence showing that NXN/FLII/actin complex is involved in ALD progression and that NXN might be involved in the regulation of FLII/actin-dependent cellular functions. Moreover, we present a promising first approach of a multi-hit protocol to better recapitulate ALD pathogenesis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Nucleoredoxin interaction with flightless‐I/actin complex is differentially altered in alcoholic liver disease

Alarcón-Sánchez

Guerrero-Escalera

Rosas-Madrigal

et al. 2020

Basic Clin Pharma Tox

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“…Lipopolysaccharide and EtOH concentrations were chosen from a report by Arellanes‐Robledo et al (2018) that demonstrated that LPS at 1 µg/mL and EtOH at 100 mmol/L in these cells produced a suitable response to investigate compounds with putative immunomodulatory activity such as SVT …”

Section: Methodsmentioning

confidence: 99%

“…A no template control, a target reagent sample and a negative sample were included on the plate. GAPDH (gene ID: 24383) (Rn01775763_g1) was used as the internal control, and the relative gene expression was calculated using the Livak method, as follows:

2^{- Δ C_{t}} \{[C_{t} (experimental target gene) - C_{t} (experimental housekeeping gene)] - [C_{t} (control target gene) - C_{t} (control housekeeping gene)]\}

…”

Section: Methodsmentioning

confidence: 99%

Stevioside inhibits experimental fibrosis by down‐regulating profibrotic Smad pathways and blocking hepatic stellate cell activation

Casas‐Grajales

Alvarez-Suarez

Ramos‐Tovar

et al. 2019

Basic Clin Pharma Tox

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Liver cirrhosis is associated with increased morbidity and mortality with important health and social consequences; however, an effective treatment has not been found yet. Previous reports have shown some beneficial effects of stevioside (SVT) in different diseases, but the ability of SVT to inhibit liver cirrhosis has not been reported. Therefore, we studied the potential of this diterpenoid to inhibit liver cirrhosis induced by thioacetamide, a model that shares many similarities with the human disease, and investigated the possible underlying molecular mechanism using in vivo and in vitro approaches. Cirrhosis was induced in male Wistar rats by chronic thioacetamide administration (200 mg/kg) intraperitoneally three times per week.Rats received saline or SVT (20 mg/kg) two times daily intraperitoneally. In addition, co-cultures were incubated with either lipopolysaccharide or ethanol. Liver fibrosis, hepatic stellate cells activation, metalloproteinases activity, canonical and non-canonical Smads pathway and expression of several profibrogenic genes were evaluated. Thioacetamide activated hepatic stellate cells and distorted the liver parenchyma with the presence of abundant thick bands of collagen. In addition, thioacetamide up-regulated the protein expression of α-smooth muscle actin, transforming growth factor-β1, metalloproteinases-9,-2 and -13 and overstimulate the canonical and non-canonical Smad pathways. SVT administration inhibited all of these changes. In vitro, SVT inhibited the up-regulation of several genes implicated in cirrhosis when cells were exposed to lipopolysaccharides or ethanol. We conclude that SVT inhibited liver damage by blocking hepatic stellate cells activation, down-regulating canonical and non-canonical profibrotic Smad pathways.

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“…Among the various contributors of the liver injury, accumulation of lipids in cytoplasm of hepatocytes takes centre stage, with not only the quantity but the quality of lipids determining severity of the damage . For example, sphingolipids (SLs) components such as acid sphingomyelinase (ASM) or ceramide (Cer) act as secondary contributors to alcoholic (ASH) or non‐alcoholic steatohepatitis (NASH).…”

Section: Introductionmentioning

confidence: 99%

Acid sphingomyelinase mediates the noise‐induced liver disorder in mice

Meng

Xie

et al. 2019

Clin Exp Pharma Physio

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Summary Noise‐induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over‐activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20–20k Hz, 90–110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.

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Ethanol targets nucleoredoxin/dishevelled interactions and stimulates phosphatidylinositol 4-phosphate production in vivo and in vitro

Cited by 14 publications

References 53 publications

Nucleoredoxin interaction with flightless‐I/actin complex is differentially altered in alcoholic liver disease

Nucleoredoxin interaction with flightless‐I/actin complex is differentially altered in alcoholic liver disease

Stevioside inhibits experimental fibrosis by down‐regulating profibrotic Smad pathways and blocking hepatic stellate cell activation

Acid sphingomyelinase mediates the noise‐induced liver disorder in mice

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