Akt Cys-310-targeted Inhibition by Hydroxylated Benzene Derivatives Is Tightly Linked to Their Immunosuppressive Effects
- Authors
- Lee, Ji Yeon; Lee, Yong Gyu; Lee, Jaehwi; Yang, Keum-Jin; Kim, Ae Ra; Kim, Joo Young; Won, Moo-Ho; Park, Jongsun; Yoo, Byong Chul; Kim, Sanghee; Cho, Won-Jea; Cho, Jae Youl
- Issue Date
- 26-Mar-2010
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.285, no.13, pp 9932 - 9948
- Pages
- 17
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 285
- Number
- 13
- Start Page
- 9932
- End Page
- 9948
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22558
- DOI
- 10.1074/jbc.M109.074872
- ISSN
- 0021-9258
1083-351X
- Abstract
- The hydroxylated benzene metabolite hydroquinone (HQ) is mainly generated from benzene, an important industrial chemical, and is also a common dietary component. Although numerous reports have addressed the tumorigenesis-inducing effects of HQ, few papers have explored its molecular regulatory mechanism in immunological responses. In this study we characterized Akt (protein kinase B)-targeted regulation by HQ and its derivatives, in suppressing inflammatory responses using cellular, molecular, biochemical, and immunopharmacological approaches. HQ down-regulated inflammatory responses such as NO production, surface levels of pattern recognition receptors, and cytokine gene expression with IC50 values that ranged from 5 to 10 mu M. HQ inhibition was mediated by blocking NF-kappa B activation via suppression of its translocation pathway, which is composed of Akt, I kappa B alpha kinase beta, and I kappa B alpha. Of the targets in this pathway, HQ directly targeted and bound to the sulfhydryl group of Cys-310 of Akt and sequentially interrupted the phosphorylation of both Thr-308 and Ser-473 by mediation of beta-mercaptoethanol, according to the liquid chromatography/mass spectroscopy analysis of the interaction of HQ with an Akt-derived peptide. Therefore, our data suggest that Akt and its target site Cys-310 can be considered as a prime molecular target of HQ-mediated immunosuppression and for novel anti Akt-targeted immunosuppressive drugs.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/22558)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.