Selenium status as determinant of connexin-43 dephosphorylation in ex vivo ischemic/reperfused rat myocardium.
Recent studies have demonstrated that electrical uncoupling at gap junctions during ischemia is associated with cardiac Connexin-43 (Cx43) dephosphorylation. Whether oxidative stress is involved in this phenomenon still remains unclear. In the present study, we examined the influence of selenium intake on reperfusion-induced Cx43 dephosphorylation. Male Wistar rats were fed a diet containing either 0.05 mg/kg (Low-Se, n = 13) or 1.5 mg/kg (High-Se, n = 11) selenium for 8 weeks. At the end of this diet, hearts were isolated and subjected to 10 min regional ischemia followed by 10 min reperfusion. The level of dephosphorylated Cx43 was determined in tissue samples from ischemic/reperfused and non-ischemic regions of the hearts. At the end of the experiemental diet, the activity of the antioxidant enzyme glutathione peroxidase (GSH-Px) was increased in high-Se hearts compared with low-Se hearts (+ 13%; p < 0.05). After ischemia/reperfusion, in low-Se hearts, Cx43 dephosphorylation appeared significantly increased in the left ventricle compared to the non-ischemic right ventricle (+ 149%; p < 0.05). The high-Se diet significantly reduced Cx43 dephosphorylation in the left ventricle (p < 0.05 vs. low-Se diet). In conclusion, our results suggest that oxidative stress may be involved in Cx43 dephosphorylation during myocardial ischemia/reperfusion, thereby contributing to arrhythmogenesis.
Rakotovao
Andry
A
Laboratoire NVMC-EA 3746, IFRT 130 Ingénierie pour le Vivant, Bâtiment Jean Roget-Domaine de la Merci, Université Joseph Fourier, 38700 La Tronche, France.
Tanguy
Stéphane
S
Toufektsian
Marie-Claire
MC
Berthonneche
Corinne
C
Ducros
Véronique
V
Tosaki
Arpad
A
de Leiris
Joël
J
Boucher
François
F
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D004032:Diet; D017629:Gap Junctions / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000378:metabolism*
D018031:Connexin 43; D005979:Glutathione Peroxidase; D012643:Selenium