Nejvíce citovaný článek - PubMed ID 16351499
Sex differences in connexin-43 expression in left ventricles of aging rats
Light pollution disturbs circadian rhythm, and this can also be deleterious to the heart by increased susceptibility to arrhythmias. Herein, we investigated if rats exposed to continuous light had altered myocardial gene transcripts and/or protein expression which affects arrhythmogenesis. We then assessed if Omacor® supplementation benefitted affected rats. Male and female spontaneously hypertensive (SHR) and normotensive Wistar rats (WR) were housed under standard 12 h/12 h light/dark cycles or exposed to 6-weeks continuous 300 lux light for 24 h. Half the rats were then treated with 200 mg/100 g b.w. Omacor®. Continuous light resulted in higher male rat vulnerability to malignant ventricular fibrillation (VF). This was linked with myocardial connexin-43 (Cx43) down-regulation and deteriorated intercellular electrical coupling, due in part to increased pro-inflammatory NF-κB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ATPase transcripts. Omacor® treatment increased the electrical threshold to induce the VF linked with amelioration of myocardial Cx43 mRNA and Cx43 protein levels and the suppression of NF-κB and iNOS. This indicates that rat exposure to continuous light results in deleterious cardiac alterations jeopardizing intercellular Cx43 channel-mediated electrical communication, thereby increasing the risk of malignant arrhythmias. The adverse effects were attenuated by treatment with Omacor®, thus supporting its potential benefit and the relevance of monitoring omega-3 index in human populations at risk.
- Klíčová slova
- NF-κB, cardiac arrhythmias, connexin-43, iNOS, light pollution, omacor, rats,
- MeSH
- fixní kombinace léků MeSH
- fyziologický stres * MeSH
- hypertenze komplikace MeSH
- konexin 43 metabolismus MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kyselina eikosapentaenová aplikace a dávkování chemie farmakologie MeSH
- kyseliny dokosahexaenové aplikace a dávkování chemie farmakologie MeSH
- modely nemocí na zvířatech MeSH
- potkani inbrední SHR MeSH
- potkani Wistar MeSH
- potravní doplňky * MeSH
- srdce účinky léků MeSH
- srdeční arytmie komplikace patofyziologie prevence a kontrola MeSH
- světelné znečištění * MeSH
- vodní organismy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- fixní kombinace léků MeSH
- konexin 43 MeSH
- kyselina eikosapentaenová MeSH
- kyseliny dokosahexaenové MeSH
- Omacor MeSH Prohlížeč
We aimed to study the impact of altered thyroid status on myocardial expression of electrical coupling protein connexin-43 (Cx43), the susceptibility of rats to ventricular fibrillation (VF) and the effects of antioxidant-rich red palm oil (RPO). Adult male and female euthyroid, hyperthyroid (treated with T3/T4), hypothyroid (treated with methimazole) Wistar rats supplemented or not with RPO for 6 weeks were used. Function of isolated perfused heart and VF threshold were determined. Left ventricular tissue was used for assessment of mRNA and protein levels of Cx43, its phosphorylated forms and topology. Protein kinase C signaling (PKC) and gene transcripts of some proteins related to cardiac arrhythmias were assessed. Hyperthyroid state resulted in decrease of total and phosphorylated forms of Cx43 and suppression of PKC-ε expression in males and females, decrease of Cx43 mRNA in females, decrease of VF threshold and increase of functional parameters in male rat hearts. In contrast, hypothyroid status resulted in the increase of total and phosphorylated forms of Cx43, enhancement PKC-ε expression in males and females, increase of Cx43 mRNA in females, increase of VF threshold and decrease of functional parameters in male rat hearts. Function of the heart was partially normalized by RPO intake, which also enhanced myocardial Cx43 and PKC-ε expression as well as increased VF threshold in hyperthyroid male rats. We conclude that there is an inverse relationship between myocardial expression of Cx43, including its functional phosphorylated forms, and susceptibility of male rat hearts to VF in condition of altered thyroid status. RPO intake partly ameliorated adverse changes caused by excess of thyroid hormones.
- Klíčová slova
- Cardiac arrhythmias, Connexin-43, PKC, Red palm oil, Thyroid hormones,
- MeSH
- aplikace orální MeSH
- konexin 43 antagonisté a inhibitory genetika metabolismus MeSH
- krysa rodu Rattus MeSH
- messenger RNA antagonisté a inhibitory genetika metabolismus MeSH
- myokard metabolismus MeSH
- oleje rostlin aplikace a dávkování farmakologie MeSH
- palmový olej MeSH
- potkani Wistar MeSH
- srdce účinky léků MeSH
- srdeční arytmie farmakoterapie metabolismus MeSH
- štítná žláza účinky léků metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Gja1 protein, rat MeSH Prohlížeč
- konexin 43 MeSH
- messenger RNA MeSH
- oleje rostlin MeSH
- palmový olej MeSH