Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells

Abstract

CF6 causes hypertension by directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the mesenteric arteriolar network via c-Src activation.

Coupling factor 6-induced activation of ecto-F1Fo complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice

“…2h). This is consistent with our previous report that CF6 enhances Ca 2+ signalling in cultured vascular smooth muscle cells and causes vasoconstriction in the mesenteric arteriolar network via c-Src activation [21]. A high-salt diet significantly increased systolic and diastolic blood pressure by 21±3 and 17±3 mmHg, respectively, in transgenic, but not in wildtype mice (p<0.05).…”

“…2d). Recent evidence has also confirmed that the β-subunit is expressed at the surface of cultured vascular endothelial cells and smooth muscle cells [20,21]. Consistent with the distribution of ecto-F 1 F o complex, proton uptake at 15 min after injection of 3 Hlabelled water into the intraperitoneal space was increased in the aorta, kidney, skeletal muscle and liver of transgenic compared with wild-type mice (Fig.…”

“…We further showed that CF6 attenuates prostacyclin generation by inhibiting cytosolic phospholipase A 2 [30] and nitric oxide generation via upregulation of asymmetric dimethylarginine or inhibition of endothelial nitric oxide synthase phosphorylation [31,32]. CF6 also elevates arterial blood pressure and enhances angiotensin IIinduced vasoconstriction in resistance arterioles [21,33]. In transgenic mice, intracellular pH measured by 31 P-MRS was reduced in skeletal muscle and liver, a finding consistent with the distribution of the receptor of CF6, the β-subunit of the ecto-F 1 F o complex.…”

“…As shown in Fig. 5e, protons regulate cellular function by modulating the charge and structure of macromolecules, such as phosphorylation of RAC1 and dephosphorylation of insulin receptor, and also explain the activation of cSrc and p38 mitogen-activated protein kinase, the other signalling pathways of CF6 [21,32]. In clinical settings, we and others previously showed that circulating CF6 is elevated in patients with hypertension, acute myocardial infarction, end-stage renal disease, stroke and diabetes [13,14,[16][17][18], all of which predispose to the development of atherosclerosis.…”

Coupling factor 6 attenuates CXCR4 expression through the HIF-1α and c-Src pathways and promotes endothelial apoptosis and inflammation

“…Staining for apoptotic cells 10 The recognition of apoptotic nuclei in paraffin-embedded tissue sections was performed using the ApopMark™ Apoptosis Detection Kit. Briefly, after permeabilizing the samples and inactivating the endogenous peroxidase, terminal deoxynucleotidyl transferase was added to bind to exposed 3'-OH ends of DNA fragments generated in response to apoptotic signals and to catalyze the addition of biotin-labeled deoxynucleotides.…”