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

Earl Gonzales; Huazhen Chen; Richard Munuve; Tina Mehrani; Joy Britten-Webb; Amal Nadel; Hasan B. Alam; David Wherry; David Burris; Elena Koustova

doi:10.1097/01.shk.0000209522.28120.c8

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

Earl Gonzales, Huazhen Chen, Richard Munuve, Tina Mehrani, Joy Britten-Webb, Amal Nadel, Hasan B. Alam, David Wherry, David Burris, Elena Koustova^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	395-401
Number of pages	7
Journal	Shock
Volume	25
Issue number	4
DOIs	https://doi.org/10.1097/01.shk.0000209522.28120.c8
State	Published - Apr 2006
Externally published	Yes

Funding

The authors gratefully acknowledge the financial support provided by the National Natural Science Foundations of China ( 51471054 , 51161015 and 51371094 ).

Keywords

Gene expression
Hemorrhagic shock
Histone code
Histone deacetylase
Hyperacetylation
Survival
Valproic acid

ASJC Scopus subject areas

Critical Care and Intensive Care Medicine
Emergency Medicine

Access to Document

10.1097/01.shk.0000209522.28120.c8

Cite this

@article{55bc9c0382d24172a2785a26c6fd7813,

title = "Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones",

abstract = "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.",

keywords = "Gene expression, Hemorrhagic shock, Histone code, Histone deacetylase, Hyperacetylation, Survival, Valproic acid",

author = "Earl Gonzales and Huazhen Chen and Richard Munuve and Tina Mehrani and Joy Britten-Webb and Amal Nadel and Alam, {Hasan B.} and David Wherry and David Burris and Elena Koustova",

note = "Funding Information: The authors gratefully acknowledge the financial support provided by the National Natural Science Foundations of China ( 51471054 , 51161015 and 51371094 ). ",

year = "2006",

month = apr,

doi = "10.1097/01.shk.0000209522.28120.c8",

language = "English (US)",

volume = "25",

pages = "395--401",

journal = "Shock",

issn = "1073-2322",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

TY - JOUR

T1 - Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones

AU - Gonzales, Earl

AU - Chen, Huazhen

AU - Munuve, Richard

AU - Mehrani, Tina

AU - Britten-Webb, Joy

AU - Nadel, Amal

AU - Alam, Hasan B.

AU - Wherry, David

AU - Burris, David

AU - Koustova, Elena

N1 - Funding Information: The authors gratefully acknowledge the financial support provided by the National Natural Science Foundations of China ( 51471054 , 51161015 and 51371094 ).

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

KW - Gene expression

KW - Hemorrhagic shock

KW - Histone code

KW - Histone deacetylase

KW - Hyperacetylation

KW - Survival

KW - Valproic acid

UR - http://www.scopus.com/inward/record.url?scp=33646821053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646821053&partnerID=8YFLogxK

U2 - 10.1097/01.shk.0000209522.28120.c8

DO - 10.1097/01.shk.0000209522.28120.c8

M3 - Article

C2 - 16670643

AN - SCOPUS:33646821053

SN - 1073-2322

VL - 25

SP - 395

EP - 401

JO - Shock

JF - Shock

IS - 4

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this