4.5 Article

Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome

期刊

JOURNAL OF APPLIED PHYSIOLOGY
卷 112, 期 7, 页码 1157-1165

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.01166.2011

关键词

passive stiffness; muscle weakness

资金

  1. VENI from Dutch Organization for Scientific Research
  2. National Institutes of Health [RO1 AR060697]
  3. Princess Beatrix Foundation

向作者/读者索取更多资源

Ottenheijm CAC, Voermans NC, Hudson BD, Irving T, Stienen GJM, van Engelen BG, Granzier H. Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome. J Appl Physiol 112: 1157-1165, 2012. First published January 5, 2012; doi:10.1152/japplphysiol.01166.2011.-Objective: tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence leads to Ehlers-Danlos Syndrome (EDS). TNX-deficient EDS patients present with joint hypermobility and muscle weakness attributable to increased compliance of the extracellular matrix. We hypothesized that in response to the increased compliance of the extracellular matrix in TNX-deficient EDS patients, intracellular adaptations take place in the elastic properties of the giant muscle protein titin. Methods: we performed extensive single muscle fiber mechanical studies to determine active and passive properties in TNX-deficient EDS patients. Gel-electrophoresis, Western blotting, and microarray studies were used to evaluate titin expression and phosphorylation. X-ray diffraction was used to measure myofilament lattice spacing. Results: passive tension of muscle fibers from TNX-deficient EDS patients was markedly increased. Myofilament extraction experiments indicated that the increased passive tension is attributable to changes in the properties of the sarcomeric protein titin. Transcript and protein data indicated no changes in titin isoform expression. Instead, differences in posttranslational modifications within titin's elastic region were found. In patients, active tension was not different at maximal activation level, but at submaximal activation level it was augmented attributable to increased calcium sensitivity. This increased calcium sensitivity might be attributable to stiffer titin molecules. Conclusion: in response to the increased compliance of the extracellular matrix in muscle of TNX-deficient EDS patients, a marked intracellular stiffening occurs of the giant protein titin. The stiffening of titin partly compensates for the muscle weakness in these patients by augmenting submaximal active tension generation.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据