Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy

László Ligeti, Orsolya Szenczi, Christina M. Prestia, Csaba Szabo, Katalin Horváth, Zoltán L. Marcsek, Ruud G P M Van Stiphout, Natal A W Van Riel, Jorn Op Den Buijs, Ger J. Van Der Vusse, Tamás Ivanics

Research output: Contribution to journalArticle

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Abstract

The main objective of the present study was to determine alterations of calcium handling in the diabetic rat heart during the transition from adaptive to maladaptive phase of cardiomyopathy. By inhibiting the nuclear enzyme poly(ADP-ribose) polymerase (PARP), we also investigated the possible role of this enzyme in the sequence of pathological events. Six weeks after induction of type I diabetes by injection of streptozotocin in rats, the hearts were perfused according to Langendorff. Intracellular-free calcium (Ca 2+ i) levels were measured by surface fluorometry using Indo-1 AM. Cyclic changes in Ca2+ i concentrations and hemodynamic parameters were measured simultaneously. The hearts were challenged by infusion of isoproterenol. Six weeks of diabetes resulted in reduced inotropy and lusitropy. The diabetic hearts (DM) expressed a significantly elevated end-diastolic Ca2+ i level (control, 111±20 vs DM, 221±35 nM). The maximal transport capacity of SERCA2a and conductance of RyR2 were reduced. These changes were not accompanied by major alterations in the tissue content of SERCA2a, RyR2, phospholamban and Na+/Ca 2+ exchanger. In response to β-adrenergic activation, SERCA2a transport capacity and RyR2 conductance were stunted in the DM hearts. Inhibition of PARP induced minor changes in the mechanical function and calcium handling of the DM hearts. In conclusion, the observed changes in contractility and in Ca2+ i handling are most likely attributable to functional disturbances of SERCA2a and RyR2 in this transitional phase of diabetes. At this stage of diabetes, PARP does not appear to play a significant pathogenetic role in the alterations in contractile function and calcium handling.

Original languageEnglish (US)
Pages (from-to)1035-1043
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume17
Issue number6
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Diabetic Cardiomyopathies
Streptozocin
Ryanodine Receptor Calcium Release Channel
Calcium
Poly(ADP-ribose) Polymerases
Sodium-Calcium Exchanger
Fluorometry
Enzymes
Type 1 Diabetes Mellitus
Cardiomyopathies
Isoproterenol
Adrenergic Agents
Hemodynamics
Injections

Keywords

  • Cardiac function
  • Diabetes
  • Intracellular calcium handling
  • Poly(ADP-ribose) polymerase
  • RyR2
  • SERCA2A

ASJC Scopus subject areas

  • Genetics

Cite this

Ligeti, L., Szenczi, O., Prestia, C. M., Szabo, C., Horváth, K., Marcsek, Z. L., ... Ivanics, T. (2006). Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. International Journal of Molecular Medicine, 17(6), 1035-1043.

Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. / Ligeti, László; Szenczi, Orsolya; Prestia, Christina M.; Szabo, Csaba; Horváth, Katalin; Marcsek, Zoltán L.; Van Stiphout, Ruud G P M; Van Riel, Natal A W; Den Buijs, Jorn Op; Van Der Vusse, Ger J.; Ivanics, Tamás.

In: International Journal of Molecular Medicine, Vol. 17, No. 6, 06.2006, p. 1035-1043.

Research output: Contribution to journalArticle

Ligeti, L, Szenczi, O, Prestia, CM, Szabo, C, Horváth, K, Marcsek, ZL, Van Stiphout, RGPM, Van Riel, NAW, Den Buijs, JO, Van Der Vusse, GJ & Ivanics, T 2006, 'Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy', International Journal of Molecular Medicine, vol. 17, no. 6, pp. 1035-1043.
Ligeti, László ; Szenczi, Orsolya ; Prestia, Christina M. ; Szabo, Csaba ; Horváth, Katalin ; Marcsek, Zoltán L. ; Van Stiphout, Ruud G P M ; Van Riel, Natal A W ; Den Buijs, Jorn Op ; Van Der Vusse, Ger J. ; Ivanics, Tamás. / Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. In: International Journal of Molecular Medicine. 2006 ; Vol. 17, No. 6. pp. 1035-1043.
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AU - Van Stiphout, Ruud G P M

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