IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart

Abstract

Bcl-2 family proteins play a crucial role in the cytoprotective action of insulin-like growth factor-I (IGF-I) by regulating cell death signaling at the mitochondrial level. The present study examined the effect of IGF-I on the expression of Bcl-2 family proteins in the rat heart mitochondria in relation to myocardial protection against ischemia-reperfusion injury. Systemic IGF-I (1 mg) treatment in the rat increased Bcl-xL and attenuated Bax 12-24 h later in the heart mitochondria fraction. Permeability transition and cytochrome c release occurred in a Ca(2+) concentration-dependent manner in the vehicle-treated mitochondria. This was significantly inhibited by the IGF-I-pretreatment. Moreover, ATP synthesis was significantly greater in the IGF-I-pretreated mitochondria. IGF-I pretreatment 24 h before 25 min of global ischemia in the isolated rat heart model significantly improved recovery of isovolumic left ventricular function and inhibited creatine kinase release during reperfusion. This was associated with a significantly less number of terminal transferase labeling-positive myocytes and nonmyocytes 2 h after reperfusion. These results suggest that IGF-1 differentially regulates Bcl-xL and Bax in heart mitochondria, which may be causally related to myocardial protection against ischemia-reperfusion injury.

Serum Levels of Insulin Growth Factor (IGF-I) and IGF-Binding Protein Predict Risk of Second Primary Tumors in Patients with Head and Neck Cancer

“…They increase DNA synthesis and stimulate the expression of cyclin D1, which accelerates the progression of the cell cycle from G 1 to S phase (40). They also have the ability to inhibit apoptosis by modulating the expression of Bcl and Bax, thereby increasing the amount of Bcl/Bax heterodimers, which are required for the initiation of apoptosis (41). Limited evidence suggests that the effects of IGF-I might also be related to p53 mutations.…”

Role of Apoptosis Signal-Regulating Kinase-1-c-Jun NH2-Terminal Kinase-p38 Signaling in Voltage-Gated K+Channel Remodeling of the Failing Heart: Regulation by Thioredoxin

“…Thus, we examined the electrophysiological role of insulin-like growth factor-1 (IGF-1) in the present study since this growth factor has been shown to exert significant antioxidant and antiapoptotic effects on the myocardium (18,36,39,44). As shown in Figure 3A, 10 nM IGF-1 for 4-5 h upregulated I to density in myocytes from MI hearts (filled squares) to a similar extent as JNK=p38 inhibitors.…”

Exercise training enhanced SIRT1 longevity signaling replaces the IGF1 survival pathway to attenuate aging-induced rat heart apoptosis

“…These multiple protein regulations contain phosphatidylinositol 3-kinase (PI3K), Akt, protein kinase B (PKB), and calcium ions (Catalucci and Condorelli 2006;Khoynezhad et al 2004;Lai et al 2003;Latronico et al 2004). Animal experiments have confirmed that IGF1 in the heart increases anti-apoptotic protein (Bcl-xL) mitochondrial performance in vivo (Yamamura et al 2001). Over-expression of cardiac-specific IGF1 (Torella et al 2004) has an effect on anti-apoptosis.…”