Cardiac protection by mitoK(ATP) channels is dependent on akt translocation from cytosol to mitochondria during late preconditioning
Yükleniyor...
Dosyalar
Tarih
2006
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Amer Physiological Soc
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
This investigation elucidates the Akt/mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel signaling pathway in late pharmacological preconditioning, using the mitoK(ATP) channel openers BMS-191095 (BMS) and diazoxide (DE). BMS (1 mg/kg ip) and DE (7 mg/kg ip) alone or BMS plus wortmannin (WTN, 15 mu g/kg ip), an inhibitor of phosphatidylinositol 3-kinase, and BMS plus 5-hydroxydecanoic acid (5-HD, 5 mg/kg ip), an inhibitor of mitoK(ATP) channels, were administered to male mice. Twenty-four hours later, hearts were isolated and subjected to 40 min of ischemia and 120 min of reperfusion via Langendorff's apparatus. Both BMS and DE reduced left ventricular end-diastolic pressure and increased left ventricular developed pressure as well as reduced LDH release. Coadministration of BMS and WTN abolished the beneficial effects of BMS on cardiac function. Moreover, BMS and DE accelerated Akt phosphorylation in cardiac tissue as determined by Western blot analysis and also significantly reduced apoptosis compared with ischemic control. WTN significantly suppressed BMS-induced Akt phosphorylation, whereas 5-HD had no effect on Akt phosphorylation in cytosol, and the effect of BMS on apoptosis was abolished. It is concluded that the cardioprotective effect by mitoK(ATP) channels is attributed to the translocation of phosphorylated Akt from cytosol to mitochondria.
Açıklama
Anahtar Kelimeler
BMS-191095, Diazoxide, Apoptosis, Mitochondrial ATP-sensitive K Channels
Kaynak
American Journal Of Physiology-Heart And Circulatory Physiology
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
290
Sayı
6
