scholarly journals Protein Tyrosine Phosphatase 1B is a negative regulator of alpha‐adrenergic vasoconstriction in mouse aorta

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Eric Belin Chantemele ◽  
Pimonrat Ketsawatsomkron ◽  
Mario Marrero ◽  
David Stepp
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Mouse Aorta

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.

Abstract 321: Protein Tyrosine Phosphatase 1B: a Novel Regulator of Proliferation and Apoptosis in the Development of Pulmonary Arterial Hypertension

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shayan Moazeni ◽  
Gregoire Ruffenach ◽  
Shervin Sarji ◽  
Christine Cunningham ◽  
Mylene Vaillancourt ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Protein Tyrosine Phosphatase ◽  
Vascular Remodeling ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Pulmonary Vascular Remodeling ◽  
Protein Tyrosine ◽  
Pulmonary Arterial

Background: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling that leads to an increase in pulmonary arterial pressure resulting in right ventricle failure and death. PAH is driven by pulmonary artery smooth muscle cell (PASMC) proliferation and resistance to apoptosis. Protein Tyrosine Phosphatase 1B (PTP1B), a negative regulator for platelet-derived growth factor (PDGF) and BCL-2, has recently been implicated in PAH in humans. While PDGF and BCL-2 are increased in PAH patients, the pathway for regulating BCL-2 and PDGF is poorly understood. We aim to investigate if PTP1B has a role in proliferation and resistance to apoptosis in PAH in human PACMCs and in the Sugen/Hypoxia/Normoxia (Su/Hx/Nx) PH rat model. Method: Adult male Sprague-Dawley rats were treated with single intraperitoneal dose of SU5416 (20 mg/kg) and kept in Hx for 3 weeks followed by Nx for 2 weeks. Saline treated rats kept in Nx for 5 weeks served as control (n=4/group). RV catheterization was performed terminally for recording RV systolic pressure (RVSP). RV, LV, and interventricular septum (IVS) were isolated for Fulton index (FI, RV/IVS+LV). We analyzed gene expression in lungs via qPCR. Healthy hPASMCs were incubated with a PTP1B inhibitor (Ethyl-3,4-dephostatin) at IC50=0.58ug/ml for 24hrs under Nx conditions and cells were stained with Ki67 to assess proliferation. Results: Su/Hx/Nx rats had severe PH evidenced by a significantly elevated RVSP compared to control (88.97+/- 13.67 vs 28.47+/- 2.22 mmHg, p<0.05). PH rats also showed severely reduced RV function and increased RV hypertrophy (FI= 0.7+/- 0.063 vs 0.274 +/-0.01, p<0.05). PH lungs exhibited severe pulmonary vascular remodeling with excessive growth of the PASMCs. PTP1B was significantly decreased in PH lungs compared to controls (0.158+/-0.0647 vs 1+/-0.06, P<0.05). BCL-2 expression was significantly increased in PAH compared to control (2.01+/-0.162 vs 1 +/-0.1, P<0.01). Inhibition of PTP1B in cultured hPASMCs increased proliferation by ~2 fold as assessed by Ki67 positive cells (n=3). Conclusion: Severe angioproliferative PH in rats is associated with a downregulation of PTP1B and increased expression of BCL-2 and PASMC proliferation.

scholarly journals Pharmacological Effects of JTT-551, a Novel Protein Tyrosine Phosphatase 1B Inhibitor, in Diet-Induced Obesity Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Makoto Ito ◽  
Sumiaki Fukuda ◽  
Shohei Sakata ◽  
Hisayo Morinaga ◽  
Takeshi Ohta
Keyword(s):  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Single Administration ◽  
Leptin Signaling ◽  
Protein Tyrosine ◽  
Diet Induced Obesity ◽  
Stat3 Phosphorylation

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin signaling as well as insulin signaling. JTT-551 is a new PTP1B inhibitor, which is reported to improve glucose metabolism by enhancement of insulin signaling. We have evaluated an antiobesity effect of JTT-551 using diet-induced obesity (DIO) mice. A single administration of JTT-551 was provided to DIO mice with or without leptin, and DIO mice were given food containing JTT-551 for six weeks. A single administration of JTT-551 with leptin treatment enhanced the food inhibition and the signal transducer and activator of transcription 3 (STAT3) phosphorylation in hypothalamus. Moreover, chronic administration of JTT-551 showed an antiobesity effect and an improvement of glucose and lipid metabolism in DIO mice. JTT-551 shows an antiobesity effect possibly by enhancement of leptin signaling and could be useful in the treatment of type 2 diabetes and obesity.

scholarly journals Therapeutic Role of Protein Tyrosine Phosphatase 1B in Parkinson’s Disease via Antineuroinflammation and Neuroprotection In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Chien-Wei Feng ◽  
Nan-Fu Chen ◽  
Te-Fu Chan ◽  
Wu-Fu Chen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Neuronal Damage ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Arginase 1

Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases. However, the currently available treatments could only relieve symptoms. Novel therapeutic targets are urgently needed. Several previous studies mentioned that protein tyrosine phosphatase 1B (PTP1B) acted as a negative regulator of the insulin signal pathway and played a significant role in the inflammation process. However, few studies have investigated the role of PTP1B in the central nervous system. Our study showed that suramin, an inhibitor of PTP1B, could improve neuronal damage. It could significantly attenuate the interferon-gamma-induced upregulation of proinflammatory cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). It enhanced M2 type microglia markers, such as arginase-1 and Ym-1 in BV2 murine microglial cells. PTP1B inhibition also reversed 6-hydroxydopamine- (6-OHDA-) induced downregulation of phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. Besides, we knocked down and overexpressed PTP1B in the SH-SY5Y cells to confirm its role in neuroprotection. We also verified the effect of suramin in the zebrafish PD model. Treatment with suramin could significantly reverse 6-OHDA-induced locomotor deficits and improved tyrosine hydroxylase (TH) via attenuating endoplasmic reticulum (ER) stress biomarkers. These results support that PTP1B could potentially regulate PD via antineuroinflammation and antiapoptotic pathways.

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.

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