Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

Karimian, Golnar; Buist‐Homan, Manon; Mikus, Bojana; Henning, Robert H.; Faber, Klaas Nico; Moshage, Han

doi:10.1371/journal.pone.0052647

Cited by 9 publications

(4 citation statements)

References 65 publications

(80 reference statements)

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“…Liver damage mainly occurs due to viral infections, excessive alcohol consumption, autoimmune reactions or as a consequence of adverse drug effects. Following liver tissue damage, HSCs undergo a transition from a quiescent to an activated phenotype and increase proliferation and synthesis of the ECM (21)(22)(23). Activated HSCs express MMPs, the key enzyme in the degradation of ECM; however, they also express TIMPs.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells

Zhang

Wang

2013

Molecular Medicine Reports

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Matrix metalloproteinase-13 (MMP-13) is crucial in the cleavage and remodeling of the extracellular matrix (ECM), and its expression levels are decreased following the induction of liver fibrosis. The aim of the present study was to investigate the role of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in interleukin (IL)-1β-mediated MMP-13 gene expression in rat hepatic stellate cells (HSCs). In the present study, we demonstrated that IL-1β is capable of activating JNK and p38 in a time-dependent manner and the inhibition of the JNK pathway is able to increase MMP-13 mRNA expression; however, the inhibition of the p38 MAPK pathway is capable of inhibiting MMP-13 gene expression. These data demonstrate that IL-1β is able to promote MMP-13 mRNA expression in rat HSCs and the JNK and p38 MAPK pathways were involved in this process. In summary, IL-1β-induced MMP-13 mRNA expression is possibly mediated by cytoplasmic JNK and p38 MAPK pathways, and they play a distinct role in this process. Thus, the JNK and p38 MAPK pathway co-operatively mediate MMP-13 mRNA expression in rat HSCs.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells

Zhang

Wang

2013

Molecular Medicine Reports

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“…The hippocampus is a key neural region involved in these diseases 28. In addition, previous studies suggest that hypertension is one of primary factors leading to apoptosis and neurodegeneration 29,30. Therefore, the ANG II-induced hypertensive mouse model was used in this study to investigate the functions of miR-195 and sirt3 in hippocampal apoptosis and associated behavioral influence.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-195-Sirt3 Axis Regulates Angiotensin II-Induced Hippocampal Apoptosis and Learning Impairment in Mice</p>

Fan¹,

Xiao²,

Zhang³

et al. 2019

PRBM

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ObjectiveApoptosis plays an essential role in cell development and aging, which is associated with a series of diseases, such as neurodegeneration. MircoRNAs exert important roles in the regulation of gene expression. As a stress-responsive deacetylase in mitochondria, sirtuin-3 (sirt3) is a key regulator for mitochondrial function and apoptosis. Also, miR-195 has been demonstrated to be involved in cell cycle and apoptosis. Therefore, this study aimed to investigate the effects of miR-195-sirt3 axis on angiotensin II (ANG II)-induced hippocampal apoptosis and behavioral influence.Materials and methodsANG II infusion was used to establish the hypertensive model in HT22 cells and 129S6/SvEvTac mice, respectively. TUNEL assay was used to evaluate the apoptosis level. Mitochondrial membrane potential (MMP) was measured to evaluate the mitochondrial property. Immunohistochemistry, RT-PCR, Western blotting, and luciferase reporter assay were conducted to determine the underlying molecular mechanism.ResultsThe results revealed that ANG II treatment promoted apoptosis in the hippocampal cells and tissues, along with increased sirt3 and decreased miR-195 expression. Silencing sirt3 by genetic engineering or siRNA reversed ANG II-induced hippocampal apoptosis. Sirt3 was identified as a direct target gene of miR-195. Forced expression of miR-195 could play counteractive roles in hippocampal apoptosis induced by ANG II. Furthermore, the behavioral assay demonstrated that ANG II-induced hippocampal apoptosis impaired the performance in the spatial navigation task, but not in the spatial memory task.ConclusionThe results suggested that miR-195-sirt3 axis plays an important role in the ANG II-induced hippocampal apoptosis via altering mitochondria-apoptosis proteins and mitochondria permeability and that hippocampal apoptosis is associated with impaired learning capability in hypertensive mice. This study provides insights into the molecular architecture of apoptosis-related neurodegenerative diseases.

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“…Following the loss of liver synthesis and excretory functions, the levels of bile salts significantly increase in patients with liver failure. In initial studies, bile salts were viewed as intervention targets ( 28 , 29 ), however, the results were not satisfactory. LPS is the main component of the gram-negative bacterial cell wall and is associated with various biological effects ( 30 , 31 ).…”

Section: Discussionmentioning

confidence: 99%

Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis

Wang

Tian

2013

Experimental and Therapeutic Medicine

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The pathogenesis of acute liver failure has not been fully elucidated. The present study investigated the effects of the serum from patients with hepatitis E virus (HEV)-related acute liver failure on human liver cell survival and apoptosis, and evaluated the protective effects of anti-lipopolysaccharide(LPS) antibody recognizing core polysaccharide against acute liver failure serum-induced apoptosis. Serum was collected from patients with HEV-related acute liver failure. The levels of endotoxin (LPS) in the serum were measured using a quantitative tachypleus amebocyte lysate endotoxin detection kit with a chromogenic endpoint. Serum with a mean concentration of LPS was incubated with L02 human liver cells and the rate of apoptosis was detected by flow cytometry. The apoptotic rate was also evaluated in liver cells incubated with antibody and the HEV-related acute liver failure serum. The results indicated that the concentration of LPS in the serum of patients with HEV-related acute liver failure was 0.26±0.02 EU/ml, which was significantly higher than that of the control group (P<0.05). The rate of apoptosis in the human liver cells induced by acute liver failure serum was 5.83±0.42%, which was significantly increased compared with that in the cells treated with the serum of healthy individuals (P<0.05). The apoptotic rate of the cells incubated with antibody and the acute liver failure serum was 5.53±0.51%, which was lower than that of the cells incubated with acute liver failure serum alone (P>0.05). These results indicate that the serum of patients with HEV-related acute liver failure induces the apoptosis of human liver cells. LPS may be directly involved in the apoptosis of human liver cells. Moreover, the presence of the antibody did not significantly reduce the level of apoptosis of liver cells exposed to HEV-related acute liver failure serum.

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Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

Cited by 9 publications

References 65 publications

Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells

Interleukin-1β upregulates matrix metalloproteinase-13 gene expression via c-Jun N-terminal kinase and p38 MAPK pathways in rat hepatic stellate cells

<p>miR-195-Sirt3 Axis Regulates Angiotensin II-Induced Hippocampal Apoptosis and Learning Impairment in Mice</p>

Serum from patients with hepatitis E virus-related acute liver failure induces human liver cell apoptosis

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