Quantitative Proteomics Reveals Transforming Growth Factor β Receptor Targeted by Resveratrol and Hesperetin Coformulation in Endothelial Cells

Abstract

The endothelium is the frontline target of multiple metabolic stressors and pharmacological agents. As a consequence, endothelial cells (ECs) display highly dynamic and diverse proteome profiles. We describe here the culture of human aortic ECs from healthy and type 2 diabetic donors, the treatment with a small molecular coformulation of trans-resveratrol and hesperetin (tRES+HESP), followed by proteomic analysis of whole-cell lysate. A number of 3666 proteins were presented in all of the samples and thus further analyzed. We found that 179 proteins had a significant difference between diabetic ECs vs. healthy ECs, while 81 proteins had a significant change upon the treatment of tRES+HESP in diabetic ECs. Among them, 16 proteins showed a difference between diabetic ECs and healthy ECs and the difference was reversed by the tRES+HESP treatment. Follow-up functional assays identified activin A receptor-like type 1 and transforming growth factor β receptor 2 as the most pronounced targets suppressed by tRES+HESP in protecting angiogenesis in vitro . Our study has revealed the global differences in proteins and biological pathways in ECs from diabetic donors, which are potentially reversible by the tRES+HESP formula. Furthermore, we have identified the TGFβ receptor as a responding mechanism in ECs treated with this formula, shedding light on future studies for deeper molecular characterization.

Impact of Protein Phosphatase Expressions on the Prognosis of Hepatocellular Carcinoma Patients

“…Researchers have identified many protein kinases, classifying them into protein tyrosine kinases and protein serine–threonine kinases. Protein serine/threonine phosphatases and protein tyrosine phosphatases (PTPs) constitute the two major classes of protein phosphatases . The human genome sequence contains a total 25,000 proteins, with 518 total protein kinases (385 protein serine/threonine kinase, 90 protein tyrosine kinase, and 43 PTK-like protein) and 119 total protein phosphatases (21 protein serine/threonine phosphatase and 98 protein tyrosine-specific phosphatase) …”

“…Compounds that bind to the catalytic site would indiscriminately affect all PP1 holoenzymes, potentially even impacting other closely related phosphatases like protein phosphatase 2A (PP2A) and PP2B holoenzymes. Conversely, substances that perturb specific PP1 holoenzymes would selectively alter PP1 activity toward a restricted set of substrates. , …”

“…Some of these inhibitors are currently undergoing clinical trials. For instance, small-molecule inhibitors targeting vascular endothelial PTP and protein tyrosine phosphatase 1B (PTP1B) are being tested for the treatment of conditions like diabetic macular edema and metastatic breast cancer, respectively. , …”

“…Conversely, substances that perturb specific PP1 holoenzymes would selectively alter PP1 activity toward a restricted set of substrates. 7 , 15 …”