Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling

Péter Kemecsei, Zsuzsanna Miklós, T. Bíró, Rita Marincsák, Balázs I. Tóth, Edina Komlódi-Pásztor, Enikó Barnucz, Éva Mirk, Ger J. Van Der Vusse, László Ligeti, Tamás Ivanics

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The muscle Lim protein knock-out (MLP-KO) mouse model is extensively used for studying the pathophysiology of dilated cardiomyopathy. However, explanation is lacking for the observed long survival of the diseased mice which develop until adulthood despite the gene defect, which theoretically predestines them to early death due to heart failure. We hypothesized that adaptive changes of cardiac intracellular calcium (Ca i 2+ ) handling might explain the phenomenon. In order to study the progression of changes in cardiac function and Ca i 2+ cycling, myocardial Ca i 2+ -transients recorded by Indo-1 surface fluorometry were assessed with concomitant measurement of hemodynamic performance in isolated Langendorff-perfused hearts of 3- and 9-month old MLP-KO animals. Hearts were challenged with β-agonist isoproterenol and the sarcoplasmic reticular Ca2+-ATPase (SERCA2a) inhibitor cyclopiazonic acid (CPA). Cardiac mRNA content and levels of key Ca2+ handling proteins were also measured. A decline in lusitropic function was observed in 3-month old, but not in 9-month old MLP-KO mice under unchallenged conditions. β-adrenergic responses to isoproterenol were similar in all the studied groups. The CPA induced an increase in end-diastolic Ca i 2+ -level and a decrease in Ca2+-sequestration capacity in 3-month old MLP-KO mice compared to age-matched controls. This unfavorable condition was absent at 9 months of age. SERCA2a expression was lower in 3-month old MLP-KO than in the corresponding controls and in 9-month old MLP-KO hearts. Our results show time-related recovery of hemodynamic function and an age-dependent compensatory upregulation of Ca i 2+ handling in hearts of MLP-KO mice, which most likely involve the normalization of the expression of SERCA2a in the affected hearts.

Original languageEnglish
Pages (from-to)251-260
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume342
Issue number1-2
DOIs
Publication statusPublished - Sep 2010

Fingerprint

Muscle Proteins
Knockout Mice
Muscle
Myocardium
Calcium
Calcium-Transporting ATPases
Proteins
Isoproterenol
Hemodynamics
Fluorometry
Recovery of Function
Dilated Cardiomyopathy
Adrenergic Agents
Up-Regulation
Heart Failure
Animals
Genes
Messenger RNA
Recovery
Defects

Keywords

  • Ca handling
  • Isolated hearts
  • MLP-KO

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kemecsei, P., Miklós, Z., Bíró, T., Marincsák, R., Tóth, B. I., Komlódi-Pásztor, E., ... Ivanics, T. (2010). Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling. Molecular and Cellular Biochemistry, 342(1-2), 251-260. https://doi.org/10.1007/s11010-010-0492-8

Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling. / Kemecsei, Péter; Miklós, Zsuzsanna; Bíró, T.; Marincsák, Rita; Tóth, Balázs I.; Komlódi-Pásztor, Edina; Barnucz, Enikó; Mirk, Éva; Van Der Vusse, Ger J.; Ligeti, László; Ivanics, Tamás.

In: Molecular and Cellular Biochemistry, Vol. 342, No. 1-2, 09.2010, p. 251-260.

Research output: Contribution to journalArticle

Kemecsei, P, Miklós, Z, Bíró, T, Marincsák, R, Tóth, BI, Komlódi-Pásztor, E, Barnucz, E, Mirk, É, Van Der Vusse, GJ, Ligeti, L & Ivanics, T 2010, 'Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling', Molecular and Cellular Biochemistry, vol. 342, no. 1-2, pp. 251-260. https://doi.org/10.1007/s11010-010-0492-8
Kemecsei, Péter ; Miklós, Zsuzsanna ; Bíró, T. ; Marincsák, Rita ; Tóth, Balázs I. ; Komlódi-Pásztor, Edina ; Barnucz, Enikó ; Mirk, Éva ; Van Der Vusse, Ger J. ; Ligeti, László ; Ivanics, Tamás. / Hearts of surviving MLP-KO mice show transient changes of intracellular calcium handling. In: Molecular and Cellular Biochemistry. 2010 ; Vol. 342, No. 1-2. pp. 251-260.
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