Bioorganic & Medicinal Chemistry Letters 2007-08-15

Induction of GRP78 by valproic acid is dependent upon histone deacetylase inhibition.

Yuanyuan Shi, David Gerritsma, Anna J Bowes, Alfredo Capretta, Geoff H Werstuck

Index: Bioorg. Med. Chem. Lett. 17 , 4491-4, (2007)

Full Text: HTML

Abstract

Valproic (2-propylpentanoic) acid is a commonly used drug in the treatment of bipolar disorder and epilepsy. The molecular mechanism that underlies its clinical efficacy remains controversial and is complicated by the broad range of intracellular effects of valproic acid, including its ability to inhibit histone deacetylase (HDAC) and induce protein chaperone expression. Here we show that an established HDAC inhibitor, trichostatin A, promotes ER chaperone expression in HEK293 cells. Furthermore, we use chemical derivatives of valproic acid to show that the ability to promote GRP78 levels directly correlates with the induction of histone H4 hyperacetylation. These results suggest that exposure to valproic acid enhances chaperone expression by a mechanism that involves histone hyperacetylation.

Related Compounds

  • 4-Phenylbutyric ac...
  • 2-Ethylbutanoic ac...
  • Valproic acid

Related Articles:

Total Analysis of Microcystins in Fish Tissue Using Laser Thermal Desorption-Atmospheric Pressure Chemical Ionization-High-Resolution Mass Spectrometry (LDTD-APCI-HRMS).

2015-08-26

[J. Agric. Food Chem. 63 , 7440-9, (2015)]

Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

2011-12-01

[J. Sci. Ind. Res. 65(10) , 808, (2006)]

Different dose-dependent mechanisms are involved in early cyclosporine a-induced cholestatic effects in hepaRG cells.

2014-09-01

[Toxicol. Sci. 141(1) , 244-53, (2014)]

The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.

2015-01-01

[Biochim. Biophys. Acta 1853(1) , 213-21, (2015)]

Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.

2015-03-20

[Oncotarget 6(8) , 6406-21, (2015)]

More Articles...