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Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice.

Publication ,  Journal Article
McKee, LAK; Chen, H; Regan, JA; Behunin, SM; Walker, JW; Walker, JS; Konhilas, JP
Published in: Archives of biochemistry and biophysics
July 2013

The pathological progression of hypertrophic cardiomyopathy (HCM) is sexually dimorphic such that male HCM mice develop phenotypic indicators of cardiac disease well before female HCM mice. Here, we hypothesized that alterations in myofilament function underlies, in part, this sex dimorphism in HCM disease development. Firstly, 10-12month female HCM (harboring a mutant [R403Q] myosin heavy chain) mice presented with proportionately larger hearts than male HCM mice. Next, we determined Ca(2+)-sensitive tension development in demembranated cardiac trabeculae excised from 10-12month female and male HCM mice. Whereas HCM did not impact Ca(2+)-sensitive tension development in male trabeculae, female HCM trabeculae were more sensitive to Ca(2+) than wild-type (WT) counterparts and both WT and HCM males. We hypothesized that the underlying cause of this sex difference in Ca(2+)-sensitive tension development was due to changes in Ca(2+) handling and sarcomeric proteins, including expression of SR Ca(2+) ATPase (2a) (SERCA2a), β-myosin heavy chain (β-MyHC) and post-translational modifications of myofilament proteins. Female HCM hearts showed an elevation of SERCA2a and β-MyHC protein whereas male HCM hearts showed a similar elevation of β-MyHC protein but a reduced level of cardiac troponin T (cTnT) phosphorylation. We also measured the distribution of cardiac troponin I (cTnI) phosphospecies using phosphate-affinity SDS-PAGE. The distribution of cTnI phosphospecies depended on sex and HCM. In conclusion, female and male HCM mice display sex dimorphic myofilament function that is accompanied by a sex- and HCM-dependent distribution of sarcomeric proteins and cTnI phosphospecies.

Duke Scholars

Published In

Archives of biochemistry and biophysics

DOI

EISSN

1096-0384

ISSN

0003-9861

Publication Date

July 2013

Volume

535

Issue

1

Start / End Page

39 / 48

Related Subject Headings

  • Ventricular Myosins
  • Troponin T
  • Troponin I
  • Sex Factors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Myosin Light Chains
  • Myosin Heavy Chains
  • Myofibrils
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McKee, L. A. K., Chen, H., Regan, J. A., Behunin, S. M., Walker, J. W., Walker, J. S., & Konhilas, J. P. (2013). Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice. Archives of Biochemistry and Biophysics, 535(1), 39–48. https://doi.org/10.1016/j.abb.2012.12.023
McKee, Laurel A. K., Hao Chen, Jessica A. Regan, Samantha M. Behunin, Jeffery W. Walker, John S. Walker, and John P. Konhilas. “Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice.Archives of Biochemistry and Biophysics 535, no. 1 (July 2013): 39–48. https://doi.org/10.1016/j.abb.2012.12.023.
McKee LAK, Chen H, Regan JA, Behunin SM, Walker JW, Walker JS, et al. Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice. Archives of biochemistry and biophysics. 2013 Jul;535(1):39–48.
McKee, Laurel A. K., et al. “Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice.Archives of Biochemistry and Biophysics, vol. 535, no. 1, July 2013, pp. 39–48. Epmc, doi:10.1016/j.abb.2012.12.023.
McKee LAK, Chen H, Regan JA, Behunin SM, Walker JW, Walker JS, Konhilas JP. Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice. Archives of biochemistry and biophysics. 2013 Jul;535(1):39–48.
Journal cover image

Published In

Archives of biochemistry and biophysics

DOI

EISSN

1096-0384

ISSN

0003-9861

Publication Date

July 2013

Volume

535

Issue

1

Start / End Page

39 / 48

Related Subject Headings

  • Ventricular Myosins
  • Troponin T
  • Troponin I
  • Sex Factors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Protein Processing, Post-Translational
  • Phosphorylation
  • Myosin Light Chains
  • Myosin Heavy Chains
  • Myofibrils