Janus Kinase 2 and Tissue Inhibitor of Matrix Metalloproteinase‐1 Mediate the Protective Effects of Erythropoietin in In‐Vitro Model of Hypoxia Ischemia

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad−/−) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3–Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad−/− mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad−/−mice than in wild-type mice. Adiponectin also promotes SOCS-3–Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)–MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.

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Tissue inhibitor of matrix metalloproteinase-1 mediates erythropoietin-induced neuroprotection in hypoxia ischemia

Neurobiology of Disease ◽

10.1016/j.nbd.2011.05.020 ◽

2011 ◽

Vol 44 (1) ◽

pp. 28-37 ◽

Cited By ~ 24

Author(s):

Rhonda Souvenir ◽

Nancy Fathali ◽

Robert P. Ostrowski ◽

Tim Lekic ◽

John H. Zhang ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Tissue Inhibitor ◽

Matrix Metalloproteinase 1 ◽

Hypoxia Ischemia

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Pravastatin increases the expression of the tissue inhibitor of matrix metalloproteinase-1 and the oncogeneBaxin human aortic abdominal aneurysms

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-060 ◽

2008 ◽

Vol 86 (7) ◽

pp. 431-437 ◽

Cited By ~ 10

Author(s):

Petra J. Mateos-Cáceres ◽

Antonio J. López-Farré ◽

Pilar C. Morata ◽

Priscila Ramos-Mozo ◽

Carlos Macaya ◽

...

Keyword(s):

Matrix Metalloproteinase ◽

Apoptotic Index ◽

Tissue Inhibitor Of Metalloproteinase ◽

Tissue Inhibitor ◽

Hmg Coa Reductase ◽

Matrix Metalloproteinase 1 ◽

Abdominal Aortic ◽

Coa Reductase ◽

Metalloproteinase 9

The effect of pravastatin on matrix metalloproteinase-9 (MMP-9) and the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 was studied in explants of human abdominal aortic aneurysm (AAA) obtained from 13 patients. The effect of pravastatin on the apoptotic status of human AAA explants was also examined. Total MMP-9 content did not differ in human AAA explants incubated in vitro in the presence or absence of pravastatin (10−6mol/L) for 48 h. TIMP-1 levels were significantly increased in pravastatin-incubated AAA explants, but TIMP-2 production was not modified by pravastatin. Western blot experiments showed that, whereas Bax expression was increased in pravastatin-incubated AAA explants, the expression of Bcl-2 was not modified. On the other hand, the ratio of the expression of Bax to Bcl-2, an apoptotic index, was not modified by pravastatin. In the human AAA explants, the increase in Bax expression, but not the increase in TIMP-1 expression elicited by pravastatin, was reversed by l-mevalonate, a downstream HMG-CoA reductase metabolite, suggesting that the expression of Bax and TIMP-1 followed HMG-CoA reductase-dependent and -independent pathways, respectively. In conclusion, pravastatin increases both TIMP-1 and Bax expression in human AAA explants without changes in either MMP-9 activity or the apoptotic status.

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Protective Effects and Mechanisms of Recombinant Human Glutathione Peroxidase 4 on Isoproterenol-Induced Myocardial Ischemia Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/6632813 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Chang Liu ◽

Bozhao Li ◽

Qi Yan ◽

Shaopeng Niu ◽

Yiding Zhao ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Ischemia ◽

Glutathione Peroxidase ◽

In Vitro Model ◽

Cardiomyocyte Apoptosis ◽

Protective Effects ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Vitro Model

Ischemic heart disease (IHD) is a cardiovascular disease with high fatality rate, and its pathogenesis is closely related to oxidative stress. Reactive oxygen species (ROS) in oxidative stress can lead to myocardial ischemia (MI) injury in many ways. Therefore, the application of antioxidants may be an effective way to prevent IHD. In recent years, glutathione peroxidase 4 (GPx4) has received increasing attention due to its antioxidant effect. In a previous study, we used the new chimeric tRNAUTuT6 to express highly active recombinant human GPx4 (rhGPx4) in amber-less Escherichia coli. In this study, we established an isoproterenol- (ISO-) induced MI injury model in rats and an in vitro model to research the protective effect and mechanism of rhGPx4 on MI injury. The results showed that rhGPx4 could reduce the area of myocardial infarction and ameliorate the pathological injury of heart tissue, significantly reduce ISO-induced abnormalities on electrocardiogram (ECG) and cardiac serum biomarkers, protect mitochondrial function, and attenuate cardiac oxidative stress injury. In an in vitro model, the results also confirmed that rhGPx4 could inhibit ISO-induced oxidative stress injury and cardiomyocyte apoptosis. The mechanism of action of rhGPx4 involves not only the inhibition of lipid peroxidation by eliminating ROS but also keeping a normal level of endogenous antioxidant enzymes by eliminating ROS, thereby preventing oxidative stress injury in cardiomyocytes. Additionally, rhGPx4 could inhibit cardiomyocyte apoptosis through a mitochondria-dependent pathway. In short, rhGPx4, a recombinant antioxidant enzyme, can play an important role in the prevention of IHD and may have great potential for application.

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Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway

Fitoterapia ◽

10.1016/j.fitote.2020.104553 ◽

2020 ◽

Vol 143 ◽

pp. 104553 ◽

Cited By ~ 3

Author(s):

Agnese Gugliandolo ◽

Federica Pollastro ◽

Placido Bramanti ◽

Emanuela Mazzon

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

In Vitro Model ◽

Mtor Pathway ◽

Protective Effects ◽

Vitro Model

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Erythrocyte deformability in an in vitro model of hypoxia/reoxygenation – protective effects of superoxide dismutase and catalase

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-1992-12214 ◽

1992 ◽

Vol 12 (2) ◽

pp. 287-296

Author(s):

A. Mary ◽

C. Bonne ◽

G. Modat

Keyword(s):

Superoxide Dismutase ◽

In Vitro Model ◽

Erythrocyte Deformability ◽

Protective Effects ◽

Vitro Model ◽

Hypoxia Reoxygenation

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Low-dose lipopolysaccharide protects nerve cells against spinal cord injury via regulating the PI3K–AKT–Nrf2 signaling pathway

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0641 ◽

2021 ◽

pp. 1-9

Author(s):

Wei-Chao Li ◽

Shao-Ping Yao ◽

Jun Zhang ◽

Wei-Bing Liu ◽

Jie Liu ◽

...

Keyword(s):

Pc12 Cells ◽

In Vitro Model ◽

Low Dose ◽

Nuclear Translocation ◽

Protective Effects ◽

Expression Levels ◽

Nrf2 Signaling Pathway ◽

Cord Injury ◽

Vitro Model

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen–glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K–AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K–AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K–AKT–Nrf2 signaling pathway. Collectively, the results indicate that PI3K–AKT–Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.

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Sangiovese cv Pomace Seeds Extract-Fortified Kefir Exerts Anti-Inflammatory Activity in an In Vitro Model of Intestinal Epithelium Using Caco-2 Cells

Antioxidants ◽

10.3390/antiox9010054 ◽

2020 ◽

Vol 9 (1) ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

Gabriele Carullo ◽

Paolo Governa ◽

Umile Gianfranco Spizzirri ◽

Marco Biagi ◽

Fabio Sciubba ◽

...

Keyword(s):

In Vitro Model ◽

Fermented Milk ◽

Food Allergies ◽

Protective Effects ◽

Electric Resistance ◽

Nutrition Science ◽

Fortified Milk ◽

Inflammatory Bowel ◽

Vitro Model

Inflammatory bowel disease and food allergies are a growing topic in the field of nutrition science. Polyphenols, which are the most important secondary metabolites of plants, demonstrated to modulate the expression and/or production of numerous proteins, but also to regulate the intestinal ecosystem. In this context, our aim was the investigation of protective effects against the gastrointestinal mucosa of fortified milk kefir obtained by adding seeds extract from Sangiovese cv. Pomace. Methods: An ultrasound-assisted method was used to obtain the extracts. All the extracts were assayed for the antioxidant activity. The best extract was used as an additive of fermented milk kefir to obtain a fortified final product. Kefir samples were analyzed by NMR spectroscopy. The efficiency of the barrier functions was evaluated by measuring trans-epithelial electric resistance (TEER) using a voltmeter. Results: the enriched kefir (Ksgn) possesses higher antioxidant performances compared to the unfortified sample (Kwht). Kwht and Ksgn did not alter Caco-2 TEER in basal condition.

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