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Thyroid hormones suppress epsilon-PKC signalling, down-regulate connexin-43 and increase lethal arrhythmia susceptibility in non-diabetic and diabetic rat heart

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Lin H., Mitasikova M., Dlugosova K., Okruhlicova L., Imanaga I., Ogawa K., Weismann P., Tribulova N.

Journal of Physiology and Pharmacology

2008

tom 59

nr 2

We examined whether thyroid hormones affect myocardial -PKC signalling, downstream target substrate, connexin-43 (Cx43) and arrhythmogenesis in non-diabetic and diabetic rats. Diabetes was induced by a single streptozotocin injection (50mg/kg, i.v.). Triiodothyronine (T3) was applied by gavage (1µg/kg of body weight for 10 days) to 4 weeks and 9 weeks diabetic and age-matched non-diabetic rats. Western blot analysis of Cx43 and -PKC, immunofluorescence of Cx43, ultrastructure of cardiomyocytes and myocardial conduction velocity were performed. Isolated perfused heart preparation was used to test ventricular fibrillation susceptibility. T3 significantly decreased -PKC expression in non-diabetic and suppressed in diabetic rat heart ventricles. Decline of -PKC signalling was associated with decrease of Cx43 phosphorylation in diabetic and to a greater extent in non-diabetic rat hearts. However, conduction velocity was significantly decreased in diabetic while enhanced due to T3 and increased in non-diabetic T3-treated rat heart ventricles compared to non-treated. T3-induced down-regulation of Cx43 was associated with increased cardiac propensity to ventricular fibrillation. Findings indicate that activation of -PKC signalling linked with phosphorylation of Cx43 is one of the mechanisms involved in the adaptation of the heart to hyperglycemia. Suppression of -PKC and Cx43 phosphorylation by T3 abolish benefit of adaptation rendering the heart prone to lethal arrhythmias.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Dlugosova K.

1 Imanaga I.

1 Lin H.

1 Mitasikova M.

1 Ogawa K.

1 Okruhlicova L.

1 Tribulova N.

1 Weismann P.

1 2008

Wyniki wyszukiwania

Thyroid hormones suppress epsilon-PKC signalling, down-regulate connexin-43 and increase lethal arrhythmia susceptibility in non-diabetic and diabetic rat heart