Beta Adrenergic Receptors Stimulation Attenuates Phosphorylation of NF-κB and IκBα in Hyperglycemic Endothelial Cells

Abstract

Background/Aims: NF-κB induces transcription of a number of genes, associated with inflammation and apoptosis. In this study, we have investigated the effect of β-adrenergic receptor stimulation on NF-κB and IκBα in HUVECs. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in high and low glucose concentrations. All HUVECs were treated with different concentrations of isoproterenol and propranolol for different time periods. The analytical procedures consisted of Western Blot, ELISA, DCFH-DA and TUNEL assays. Results: Isoproterenol (agonist of a beta-adrenergic receptor) significantly reduced phosphorylation at Ser-536 of NF-κB; and Ser-32 and Ser-36 of IκBα in hyperglycemic HUVECs. Isoproterenol also significantly reduced apoptosis and ROS generation. No effect of IκBα was observed on Tyr-42 phosphorylation. The effect of isoproterenol was reversed by the antagonist propranolol. We also checked if NF-κB inhibitor MG132 causes any change at the level of apoptosis. However, we observed an almost similar effect. Conclusion: Given data demonstrates that beta-adrenergic receptors stimulation has a protective effect on HUVECs that might be occuring via NF-κβ and IκBα pathway.

Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19)

“…39 Safia and colleagues showed that, in vitro, beta-adrenergic receptor stimulation reduced EC apoptosis and decreased the level of reactive oxygen species generation via the NF-jB/IjBa pathway. 40 Their study demonstrated that hyperglycemia could be an apoptotic stimulus to trigger NF-jB release and activation. 40…”

“…40 Their study demonstrated that hyperglycemia could be an apoptotic stimulus to trigger NF-jB release and activation. 40…”

Post-translational Modifications of IκBα: The State of the Art

“…The IKK complex can be activated by lipopolysaccharides (LPSs), viral proteins, oxygen free radicals, cytokines and other stimuli; it then phosphorylates the Ser36 and Ser32 residues in the SRD region of the N-terminus of IκBα (Traenckner et al, 1995;Hayden and Ghosh, 2004;Kato et al, 2012;Ko et al, 2017;Liu et al, 2018;Safi et al, 2018), leading to ubiquitination and the subsequent degradation of the IκBα in proteasome (Figure 2). IKK-dependent IκBα phosphorylation at the serine residues occurring in the cytosol is a key step in the release of active NF-κB and its nuclear translocation (Yazdi et al, 2017).…”

The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens

“…β2ADR has been reported to enhance the anti-inflammatory properties in some organs and tissues, like immune [ 11 ], urinary [ 12 ], nervous [ 13 ], cardiovascular [ 14 ], and respiratory systems [ 10 ]. This receptor affects its mentioned functions mainly through activating the canonical signaling pathway β2ADR/ Gs protein (Gs protein, Gs)/cAMP/protein kinase A (Protein kinase A, PKA) [ 12 ].…”

“…Among these, the agonists and blockers of beta-2 adrenergic receptors have been shown to create the anti-inflammatory functions in the different tissues. On one hand, as the anti-inflammatory agents, usage of some beta-2 adrenergic agonists (Beta-2 Adrenergic Agonist, BAA) have been recommended to treat the immune, urinary, nervous, cardiovascular, and respiratory dysfunctions [ 10 – 14 ]. Beta blockers (Beta Blocker, BB), on the other hand, decrease the inflammatory signs in the diseases like rheumatoid arthritis, respiratory disorders, and cancers [ 15 – 18 ].…”