Titin-actin interaction: PEVK-actin-based viscosity in a large animal.
Titin-actin interaction: PEVK-actin-based viscosity in a large animal.
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DOI：
10.1155/2011/310791
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发表时间：
2011
影响因子：
--
通讯作者：
Granzier HL
中科院分区：
文献类型：
--
作者：
Chung CS;Bogomolovas J;Gasch A;Hidalgo CG;Labeit S;Granzier HL
Titin显示其PEVK片段与肌动蛋白细丝之间的相互作用导致粘度，这是一种速度依赖的阻力，显著影响小鼠的舒张期充盈。虽然舒张性疾病在临床上是普遍存在的，但人类表达的Titin(N2BA：N2b比率~0.5-1.0)比小鼠(N2BA：N2b比率~0.2)更具顺应性。为了检测依从性Titin组织中基于PEVK-肌动蛋白的粘度，我们使用了表达与人类相似的Titin亚型的猪心脏组织。拉伸-保持实验的速度为0.1-10个长度/S，肌节松弛长度(SL)为2.15 μm，根据应力松弛斜率与拉伸速度的关系计算粘度。重组的PEVK被加入以竞争天然的相互作用，这被发现减少了35%的斜率，这表明PEVK-肌动蛋白的相互作用是粘度的强大贡献者。频率扫描在0.1HZ-400HZ进行，重组蛋白在2.15μm和2.25μm分别降低了40%和50%的粘度，这表明粘度具有SL依赖的性质，这可能防止SL在舒张期较长的SLS时超调。这项研究首次表明，粘度在猪体内以生理速度存在，并支持PEVK-肌动蛋白相互作用在人类健康和疾病中的生理学相关性。
Titin exhibits an interaction between its PEVK segment and the actin filament resulting in viscosity, a speed dependent resistive force, which significantly influences diastolic filling in mice. While diastolic disease is clinically pervasive, humans express a more compliant titin (N2BA:N2B ratio ~0.5–1.0) than mice (N2BA:N2B ratio ~0.2). To examine PEVK-actin based viscosity in compliant titin-tissues, we used pig cardiac tissue that expresses titin isoforms similar to that in humans. Stretch-hold experiments were performed at speeds from 0.1 to 10 lengths/s from slack sarcomere lengths (SL) to SL of 2.15 μm. Viscosity was calculated from the slope of stress-relaxation vs stretch speed. Recombinant PEVK was added to compete off native interactions and this found to reduce the slope by 35%, suggesting that PEVK-actin interactions are a strong contributor of viscosity. Frequency sweeps were performed at frequencies of 0.1–400 Hz and recombinant protein reduced viscous moduli by 40% at 2.15 μm and by 50% at 2.25 μm, suggesting a SL-dependent nature of viscosity that might prevent SL “overshoot” at long diastolic SLs. This study is the first to show that viscosity is present at physiologic speeds in the pig and supports the physiologic relevance of PEVK-actin interactions in humans in both health and disease.
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影响因子：
37.8
作者：
Lewinter MM;Popper J;McNabb M;Nyland L;Bell SB;Granzier H
通讯作者：
Granzier H
影响因子：
20.1
作者：
Hidalgo C;Hudson B;Bogomolovas J;Zhu Y;Anderson B;Greaser M;Labeit S;Granzier H
通讯作者：
Granzier H
影响因子：
3.5
作者：
Kellermayer, MSZ;Granzier, HL
通讯作者：
Granzier, HL
影响因子：
20.1
作者：
Granzier HL;Radke MH;Peng J;Westermann D;Nelson OL;Rost K;King NM;Yu Q;Tschöpe C;McNabb M;Larson DF;Labeit S;Gotthardt M
通讯作者：
Gotthardt M
影响因子：
5
作者：
Chung CS;Granzier HL
通讯作者：
Granzier HL