scholarly journals βA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sayan Ghosh ◽  
Haitao Liu ◽  
Meysam Yazdankhah ◽  
Nadezda Stepicheva ◽  
Peng Shang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glucose Metabolism ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Vitreous Humor ◽  
Lens Protein ◽  
Protein Tyrosine Phosphatase 1B ◽  
Metabolic Abnormalities ◽  
Retinal Astrocytes ◽  
Uncompetitive Inhibitor

AbstractβA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as βA3 and βA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that βA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of βA3/A1-crystallin in metabolism of retinal astrocytes. We found that βA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but βA3-crystallin does not. Loss of βA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited βA1-knockdown (KD) mice, but not in βA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified βA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced βA1-crystallin and higher levels of PTP1B in the vitreous humor.

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.

The Involvement of the Mammalian Target of Rapamycin, Protein Tyrosine Phosphatase 1b and Dipeptidase 4 Signaling Pathways in Cancer and Diabetes: A Narrative Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiajia Zhang ◽  
Ning Wu ◽  
Dayong Shi
Keyword(s):  
Signaling Pathways ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mammalian Target Of Rapamycin ◽  
Eukaryotic Cell ◽  
Target Of Rapamycin ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Transduction Mechanisms ◽  
Specific Proteins

Background: The mammalian target of rapamycin (mTOR), protein tyrosine phosphatase 1b (PTP1B) and dipeptidase 4 (DPP4) signaling pathways regulate eukaryotic cell proliferation and metabolism. Previous researches described different transduction mechanisms in the progression of cancer and diabetes. Methodology: We reviewed recent advances in the signal transduction pathways of mTOR, PTP1B and DPP4 regulation and determined the crosstalk and common pathway in diabetes and cancer. Results: We showed that according to numerous past studies, the proteins participate in the signaling networks for both diseases. Conclusion: There are common pathways and specific proteins involved in diabetes and cancer. This article demonstrates and explains the potential mechanisms of association and future prospects for targeting these proteins in pharmacological studies.

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