PDK1/Akt/PDE4D axis identified as a target for asthma remedy synergistic with β2 AR agonists by a natural agent arctigenin

Allergy
Runping FangGang Bai

Abstract

Asthma is a heterogenetic disorder characterized by chronic inflammation with variable airflow obstruction and airway hyper-responsiveness. As the most potent and popular bronchodilators, β2 adrenergic receptor (β2 AR) agonists bind to the β2 ARs that are coupled via a stimulatory G protein to adenylyl cyclase, thereby improving cAMP accumulation and resulting in airway smooth muscle relaxation. We previously demonstrated arctigenin had a synergistic function with the β2 AR agonist, but the target for this remained elusive. Chemical proteomics capturing was used to enrich and uncover the target of arctigenin in human bronchial smooth muscle cells, and reverse docking and molecular dynamic stimulation were performed to evaluate the binding of arctigenin and its target. In vitro enzyme activities and protein levels were demonstrated with special kits and Western blotting. Finally, guinea pig tracheal muscle segregation and ex vivo function were analysed. Arctigenin bound to PDK1 with an ideal binding free energy -25.45 kcal/mol and inhibited PDK1 kinase activity without changing its protein level. Additionally, arctigenin reduced PKB/Akt-induced phosphorylation of PDE4D, which was first identified in this study. Attenuation of PD...Continue Reading

References

Jan 1, 1996·The Journal of Asthma : Official Journal of the Association for the Care of Asthma·D M ScalabrinC K Naspitz
Feb 18, 1999·Current Biology : CB·C BelhamJ Avruch
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·G HansenM Conti
Oct 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Céline MéhatsMarco Conti
Mar 15, 2006·Molecular & Cellular Proteomics : MCP·Bill X Huang, Hee-Yong Kim
Jul 11, 2006·Cellular Signalling·Deepak A Deshpande, Raymond B Penn
Nov 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tomoko HayashiEyal Raz
Oct 29, 2010·Inflammopharmacology·Yuk-Shing ChanShun-Wan Chan
May 3, 2011·Nature Medicine·Karen K RyanRandy J Seeley
May 17, 2011·Current Medicinal Chemistry·C Raimondi, M Falasca
Jul 5, 2011·European Journal of Heart Failure·Antoine H Chaanine, Roger J Hajjar
Jul 30, 2011·The Journal of Biological Chemistry·Peter J Barnes
Nov 22, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kyoko NiimiBrian G G Oliver
Sep 4, 2012·The New England Journal of Medicine·Huib A M KerstjensEric D Bateman
Mar 8, 2014·ACS Nano·Hyeun Joong YoonSunitha Nagrath
May 29, 2014·Expert Opinion on Investigational Drugs·Maria Gabriella MateraMario Cazzola
Jun 4, 2014·Nature Communications·Chih-Chau HwangJames M Tour
Jun 25, 2014·International Immunopharmacology·Jeffrey R Stokes
Oct 3, 2014·Annals of Thoracic Medicine·Abdullah A Alangari
Oct 9, 2014·Annual Review of Pharmacology and Toxicology·Heung-Woo ParkScott T Weiss

❮ Previous
Next ❯

Citations

Mar 17, 2015·Expert Review of Molecular Diagnostics·Sinuhe HahnNandor Gabor Than
Apr 9, 2017·Journal of Nanobiotechnology·Qingxin CuiGang Bai
Jan 11, 2019·Molecular Medicine Reports·Fen-Hong QianDan-Dan Zheng
Sep 6, 2020·International Journal of Molecular Sciences·Hui ShiHuabao Xiong
Jun 6, 2018·Frontiers in Chemistry·Hongbin HuangZunnan Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Asthma

This feed focuses in Asthma in which your airways narrow and swell. This can make breathing difficult and trigger coughing, wheezing and shortness of breath.

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.