scholarly journals Comment on ‘Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR−/− mouse model of atherosclerosis’

2018 ◽  
Vol 132 (1) ◽  
pp. 37-38 ◽  
Author(s):  
Joseph V. Moxon ◽  
Corey S. Moran ◽  
Jonathan Golledge
Keyword(s):  
Mouse Model ◽  
Atherosclerotic Plaque ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Plaque Formation ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Pharmacological Inhibition ◽  
Atherosclerotic Plaque Formation

scholarly journals Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR−/− mouse model of atherosclerosis

2017 ◽  
Vol 131 (20) ◽  
pp. 2489-2501 ◽  
Author(s):  
Dawn Thompson ◽  
Nicola Morrice ◽  
Louise Grant ◽  
 Samantha Le Sommer ◽  
Emma K. Lees ◽  
...  
Keyword(s):  
Mouse Model ◽  
Atherosclerotic Plaque ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Plaque Formation ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Cvd Risk ◽  
Protein Tyrosine ◽  
Atherosclerotic Plaque Formation

Cardiovascular disease (CVD) is the most prevalent cause of mortality among patients with type 1 or type 2 diabetes, due to accelerated atherosclerosis. Recent evidence suggests a strong link between atherosclerosis and insulin resistance, due to impaired insulin receptor (IR) signalling. Here, we demonstrate that inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B), the major negative regulator of the IR prevents and reverses atherosclerotic plaque formation in an LDLR−/− mouse model of atherosclerosis. Acute (single dose) or chronic PTP1B inhibitor (trodusquemine) treatment of LDLR−/− mice decreased weight gain and adiposity, improved glucose homeostasis and attenuated atherosclerotic plaque formation. This was accompanied by a reduction in both, circulating total cholesterol and triglycerides, a decrease in aortic monocyte chemoattractant protein-1 (MCP-1) expression levels and hyperphosphorylation of aortic Akt/PKB and AMPKα. Our findings are the first to demonstrate that PTP1B inhibitors could be used in prevention and reversal of atherosclerosis development and reduction in CVD risk.

Reduced Insulin Resistance Contributes to the Beneficial Effect of Protein Tyrosine Phosphatase-1B Deletion in a Mouse Model of Sepsis

Shock ◽  
2017 ◽  
Vol 48 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Eugénie Delile ◽  
Rémi Nevière ◽  
Pierre-Alain Thiébaut ◽  
Julie Maupoint ◽  
Paul Mulder ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mouse Model ◽  
Beneficial Effect ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

Reduction of heart failure by pharmacological inhibition or gene deletion of protein tyrosine phosphatase 1B

2012 ◽  
Vol 52 (6) ◽  
pp. 1257-1264 ◽  
Author(s):  
Elodie Gomez ◽  
Magali Vercauteren ◽  
Baptiste Kurtz ◽  
Antoine Ouvrard-Pascaud ◽  
Paul Mulder ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Tyrosine Phosphatase ◽  
Gene Deletion ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Pharmacological Inhibition ◽  
Or Gene

Abstract 3552: Pharmacological Inhibition or Genetic Disruption of Protein Tyrosine Phosphatase 1B Attenuates both Myocardial and Endothelial Dysfunction in Mice with Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Magali Vercauteren ◽  
Baptiste Kurtz ◽  
Elodie Gomez ◽  
Jean-Paul Henry ◽  
Fabrice Bauer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Left Ventricular ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Pharmacological Inhibition

We have shown previously that acute, in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B) improved endothelial function of peripheral resistance arteries in mice with chronic heart failure (CHF), as demonstrated by the restored flow-mediated, NO-dependent vasodila-tation (FMD). This is most likely due to increased tyrosine phosphorylation pathways involved in shear stress-induced activation of eNOS. The present study evaluates the impact of chronic pharmacological inhibition or genetic disruption of PTP1B, on cardiac and endothelial dysfunction in CHF mice. CHF was induced by coronary ligation, either in C57BL/6 mice, or in wild type (WT) or PTP1B-deficient (PTP1B−/−) BALB/c mice. CHF mice (either C57BL/6 or BALB/c WT) were untreated or treated with the PTP1B inhibitor AS279 (60 mg/kg/day) for 2 months. Mice were then anesthetized with isoflurane for echocardiographic evaluation of left ventricular (LV) function and remodeling. After euthanasia, small mesenteric artery segments were isolated and mounted in an arteriograph for the evaluation of FMD. Echocardiographic results are shown in the Table . In parallel, in vitro vascular studies showed that chronic AS279 restored FMD both in C57BL/6 (max FMD: control: 17±2, n=9; CHF untreated: -1±1, n=9; CHF + AS279: 14±2%, n=19; p<0.01 vs. CHF untreated) and BALB/c CHF mice (Control: 29±4, n=16; CHF untreated: 7±1, n=5; CHF + AS279: 24±6%, n=7; p<0.01 vs. CHF untreated). Compared to CHF WT, FMD was also increased in PTP1B−/− CHF mice (WT: 7±1, n=5, PTP1B−/−: 16±6%, n=6, p<0.05). Additionally, in vitro downregulation of PTP1B (by a 3 day incubation with shRNA) also increased FMD in arteries isolated from CHF mice (max FMD: untreated: 6±2; scrambled shRNA: 7±2; shRNA PTP1B: 27±2%, p<0.01). Thus, chronic pharmacological inhibition or genetic disruption of PTP1B both restores endothelial function and improves cardiac dysfunction and remodeling, suggesting that this enzyme may be a new target for the treatment of CHF. Echocardiographic results in mice with 2 months CHF

Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

2018 ◽  
Vol 17 (3) ◽  
pp. 134-139
Author(s):  
R.M. Perez-Gutierrez
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Methanol Extract ◽  
Tyrosine Phosphatase ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

Sign in / Sign up

Export Citation Format

Share Document