HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice

Takahiro Ishiwata; András Orosz; Xiaohui Wang; Soumyajit Banerjee Mustafi; Gregory W Pratt; Elisabeth S Christians; Sihem Boudina; E Dale Abel; Ivor J Benjamin

doi:10.1371/journal.pone.0042118

Back

HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice

Journal article

Open access

Peer reviewed

HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice

Takahiro Ishiwata, András Orosz, Xiaohui Wang, Soumyajit Banerjee Mustafi, Gregory W Pratt, Elisabeth S Christians, Sihem Boudina, E Dale Abel and Ivor J Benjamin

PloS one, Vol.7(8), pp.e42118-e42118

2012

DOI: 10.1371/journal.pone.0042118

PMCID: PMC3411653

PMID: 22870288

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0042118View

Published (Version of record) Open Access

Abstract

CryAB (HspB5) and HspB2, two small heat shock genes located adjacently in the vertebrate genome, are hypothesized to play distinct roles. Mice lacking both cryab and hspb2 (DKO) are viable and exhibit adult-onset degeneration of skeletal muscle but confounding results from independent groups were reported for cardiac responses to different stressful conditions (i.e., ischemia/reperfusion or pressure overload). To determine the specific requirements of HSPB2 in heart, we generated cardiac-specific HSPB2 deficient (HSPB2cKO) mice and examined their cardiac function under basal conditions and following cardiac pressure overload. Transverse aortic constriction (TAC) or sham surgery was performed in HSPB2cKO mice and their littermates (HSPB2wt mice). Eight weeks after TAC, we found that expression of several small HSPs (HSPB2, 5, 6) was not markedly modified in HSPB2wt mice. Both cardiac function and the hypertrophic response remained similar in HSPB2cKO and HSPB2wt hearts. In addition, mitochondrial respiration and ATP production assays demonstrated that the absence of HSPB2 did not change mitochondrial metabolism in basal conditions. However, fatty acid supported state 3 respiration rate (ADP stimulated) in TAC operated HSPB2cKO hearts was significantly reduced in compared with TAC operated HSPB2wt mice (10.5±2.2 vs. 12.8±2.5 nmol O(2)/min/mg dry fiber weight, P<0.05), and ATP production in HSPB2cKO hearts was significantly reduced in TAC compared with sham operated mice (29.8±0.2 vs. 21.1±1.8 nmol ATP/min/mg dry fiber weight, P<0.05). Although HSPB2 was not associated with mitochondria under cardiac stress, absence of HSPB2 led to changes in transcript levels of several metabolic and mitochondrial regulator genes. The present study indicates that HSPB2 can be replaced by other members of the multigene small HSP family under basal conditions while HSPB2 is implicated in the regulation of metabolic/mitochondrial function under cardiac stress such pressure overload.

Blood Pressure

Mitochondria, Heart - metabolism

Mitochondria, Heart - pathology

Oxygen Consumption

Adenosine Triphosphate - genetics

Cardiomegaly - pathology

Adenosine Triphosphate - biosynthesis

Mice, Knockout

Animals

Mice

Cardiomegaly - genetics

HSP27 Heat-Shock Proteins

Mitochondria, Heart - genetics

Cardiomegaly - metabolism

Details

Title: Subtitle: HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice
Creators: Takahiro Ishiwata - Laboratory of Cardiac Disease, Redox Signaling and Cell Regeneration, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
András Orosz
Xiaohui Wang
Soumyajit Banerjee Mustafi
Gregory W Pratt
Elisabeth S Christians
Sihem Boudina
E Dale Abel
Ivor J Benjamin
Resource Type: Journal article
Publication Details: PloS one, Vol.7(8), pp.e42118-e42118
DOI: 10.1371/journal.pone.0042118
PMID: 22870288
PMCID: PMC3411653
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: 1DP1OD006438-02 / NIH HHS R01 HL074370 / NHLBI NIH HHS DP1 OD006438 / NIH HHS 5R01HL074370-03 / NHLBI NIH HHS
Language: English
Date published: 2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025290502771

Metrics

26 Record Views

18 Times Cited - Web of Science