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

• Autorzy: Lin H. , Mitasikova M. , Dlugosova K. , Okruhlicova L. , Imanaga I. , Ogawa K. , Weismann P. , Tribulova N.
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

injection; myocardial conduction; ventricular fibrillation; thyroid hormone; arrhythmia; rat; lethal arrhythmia; cardiomyocyte; diabetes; connexin 43; susceptibility; heart; streptozotocin

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2008
• Tom: 59
• Numer: 2
• Opis fizyczny: p.271-285,fig.,ref.

Twórcy

autor

Lin H.

• Fukuoka University Medical School, Fukuoka, Japan

autor

Mitasikova M.

autor

Dlugosova K.

autor

Okruhlicova L.

autor

Imanaga I.

autor

Ogawa K.

autor

Weismann P.

autor

Tribulova N.