Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones

被引：70

作者：

Gonzales, E ^{[1
]}

Chen, HZ ^{[1
]}

Munuve, R ^{[1
]}

Mehrani, T ^{[1
]}

Britten-Webb, J ^{[1
]}

Nadel, A ^{[1
]}

Alam, HB ^{[1
]}

Wherry, D ^{[1
]}

Burris, D ^{[1
]}

Koustova, E ^{[1
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Dept Surg, Trauma Res & Readiness Inst Surg, Bethesda, MD 20814 USA

来源：

SHOCK | 2006年 / 25卷 / 04期

关键词：

valproic acid; hemorrhagic shock; gene expression; histone code; histone deacetylase; hyperacetylation; survival;

D O I：

10.1097/01.shk.0000209522.28120.c8

中图分类号：

R4 [临床医学];

学科分类号：

1002 [临床医学]; 100602 [中西医结合临床];

摘要：

Pharmacological inhibitors of histone deacetylases (HDAC) demonstrate cytoprotective effects both in vitro and in vivo. In this study, we investigated whether valproic acid (VPA), a known mood stabilizer and anticonvulsant with HDAC-inhibiting activity, improves survival following otherwise lethal hemorrhage in rats. We found that preinsult injection of VPA (300 mg/kg, twice) prolonged the survival of severely hypotensive animals up to 5 times. VPA treatment increased the acetylation of nonhistone and histone proteins in the rat heart. The pattern of modifications of individual histones revealed hyperacetylation of histones H2A, H3, and H4, indicating the presence of active genes. Expression of HSP70 and superoxide dismutase, implicated in the modulation of vitality, was increased by VPA. Our results reveal that VPA offers considerable protection in the hemorrhagic shock model and suggest a role for HDAC inhibition in mediating VPA actions.

引用

页码：395 / 401

页数：7

共 38 条

[1]

cDNA array analysis of gene expression following hemorrhagic shock and resuscitation in rats [J].