HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice.
HSPB2 is dispensable for the cardiac hypertrophic response but reduces mitochondrial energetics following pressure overload in mice.
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DOI：
10.1371/journal.pone.0042118
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Benjamin IJ
中科院分区：
文献类型：
--
作者：
Ishiwata T;Orosz A;Wang X;Mustafi SB;Pratt GW;Christians ES;Boudina S;Abel ED;Benjamin IJ
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 O2/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.
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影响因子：
5
作者：
Kadono, Toshie;Zhang, Xiu Quan;Benjamin, Ivor J.
通讯作者：
Benjamin, Ivor J.
影响因子：
14.8
作者：
Frezza, Christian;Cipolat, Sara;Scorrano, Luca
通讯作者：
Scorrano, Luca
DOI：
10.1016/s0141-8130(98)00013-0
发表时间：
1998-05-01
影响因子：
8.2
作者：
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通讯作者：
Leunissen, JAM
影响因子：
20.1
作者：
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通讯作者：
Wang, Xuejun
影响因子：
2.8
作者：
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通讯作者：
Urtizberea, Andoni