Michaelis, Martin, Köhler, Nezira, Reinisch, Alexander, Eikel, Daniel, Gravemann, Ute, Doerr, Hans Wilhelm, Nau, Heinz, Cinatl, Jindrich (2004) Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid. Biochemical Pharmacology, 68 (3). pp. 531-8. ISSN 0006-2952. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:34119)
The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. |
Abstract
Valproic acid (2-propylpentanoic acid, VPA), an effective inhibitor of histone deacetylases (HDAC) is used for the treatment of epilepsia. In this study, structure-activity relationships for the action of structurally modified VPA derivatives on human cytomegalovirus (HCMV) replication and HDAC inhibition were defined. Pretreatment of human foreskin fibroblasts with VPA (0.125-1mM) caused a concentration-dependent increase of HCMV immediate early and antigen late antigen expression. Structure-activity relationships of VPA derivatives for HCMV stimulation were compared to those for teratogenic action and those for HDAC inhibition. Side chain elongation and introduction of a triple bond in 4-position of the other chain caused teratogenicity, stimulated HCMV replication, and increased HDAC inhibition, as demonstrated by enhanced levels of acetylated histones. Teratogenic VPA derivatives with a branched chain in 3-position as well as a non-teratogenic anticonvulsive active VPA derivative did not stimulate HCMV or accumulation of acetylated histones. This demonstrates a strict correlation between inhibition of HDAC and increased HCMV replication.
Item Type: | Article |
---|---|
Subjects: |
Q Science > QR Microbiology > QR355 Virology R Medicine > RM Therapeutics. Pharmacology |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Depositing User: | Martin Michaelis |
Date Deposited: | 05 Jun 2013 20:19 UTC |
Last Modified: | 16 Nov 2021 10:11 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/34119 (The current URI for this page, for reference purposes) |
Michaelis, Martin: | ![]() |
- Export to:
- RefWorks
- EPrints3 XML
- BibTeX
- CSV
- Depositors only (login required):