HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice. PLoS One 2012;7(8):e42118
Date
08/08/2012Pubmed ID
22870288Pubmed Central ID
PMC3411653DOI
10.1371/journal.pone.0042118Scopus ID
2-s2.0-84864755799 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
BACKGROUND: 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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCE: 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.
Author List
Ishiwata T, Orosz A, Wang X, Mustafi SB, Pratt GW, Christians ES, Boudina S, Abel ED, Benjamin IJAuthor
Ivor J. Benjamin MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Blood Pressure
Cardiomegaly
HSP27 Heat-Shock Proteins
Mice
Mice, Knockout
Mitochondria, Heart
Oxygen Consumption
