Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Roztocil, Elisa; Nicholl, Suzanne M.

doi:10.1016/j.surg.2008.03.023

Cited by 4 publications

(5 citation statements)

References 40 publications

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“…The phosphorylation of EGFR appeared to be enhanced in the presence of GM6001, with a relatively higher S.E.M. In line with our observations, GM6001 was also reported previously as causing a slightly higher EGFR phosphorylation induced by insulin (Roztocil et al, 2008).…”

Section: Resultssupporting

confidence: 93%

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Ulu

Henning

Güner

et al. 2013

J Pharmacol Exp Ther

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Transactivation of epidermal growth factor receptor (EGFR) by a 1 -adrenoceptor (a 1 -AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all a 1 -AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster ovary (CHO) cells stably expressing one subtype of a 1 -AR were transiently transfected with EGFR. The transactivation mechanism was examined both by coexpression of a chimeric erythropoietin (EPO)-EGFR with an extracellular EPO and intracellular EGFR domain, and by pharmacologic inhibition of external and internal signaling routes. All three a 1 -AR subtypes transactivated EGFR, which was dependent on the increase in intracellular calcium. The EGFR kinase inhibitor AG1478 [4-(39-chloroanilino)-6,7-dimethoxyquinazoline] abrogated a 1A -AR and a 1D -AR induced phosphorylation of EGFR, but both the inhibition of matrix metalloproteinases by GM6001or blockade of EGFR by cetuximab did not. Stimulation of a 1A -AR and a 1D -AR also induced phosphorylation of EPO-EGFR chimeric receptors. Moreover, a 1A -AR stimulation enhanced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 and serine-threonine kinases (Akt), which were both unaffected by AG1478, indicating that ERK1/2 and Akt phosphorylation is independent of EGFR transactivation. Accordingly, inhibitors of ERK1/2 or Akt did not influence the a 1A -AR-mediated EGFR transactivation. Inhibition of calcium/ calmodulin-dependent kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K), and Src, however, did block EGFR transactivation by a 1A -AR and a 1D -AR. These findings demonstrate that all a 1 -AR subtypes transactivate EGFR, which is dependent on an intracellular signaling route involving an increase in calcium and activation of CaMKII, PI3K, and Src, but not the of ERK1/2 and Akt pathways.

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Section: Resultssupporting

confidence: 93%

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Ulu

Henning

Güner

et al. 2013

J Pharmacol Exp Ther

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“…Insulin resistance and the associated metabolic syndrome lead to a reduction in the ability of multiple cell types, and especially neurons, to uptake glucose, regulate calcium homeostasis and respond positively to trophic and neurotrophic stimuli [ 173 ]. In addition to generating a global disruption of neuronal energy balance, protracted insulin resistance leads to a loss of vascular smooth muscle cell (VSMC) functional regulation and promotion of VSMC migration [ 174 ]. The latter is crucial in atherosclerotic development and wound healing.…”

Section: Egfr Regulates Aging-related Metabolic Activitymentioning

confidence: 99%

“…The latter is crucial in atherosclerotic development and wound healing. Insulin has also been implicated in epidermal wound healing though EGFR signaling [ 174 ]. Insulin can induce transactivation of EGFR by ADAM-mediated HB-EGF-dependent process in VSMCs [ 174 ].…”

Section: Egfr Regulates Aging-related Metabolic Activitymentioning

confidence: 99%

“…Insulin has also been implicated in epidermal wound healing though EGFR signaling [ 174 ]. Insulin can induce transactivation of EGFR by ADAM-mediated HB-EGF-dependent process in VSMCs [ 174 ]. In quiescent fibroblasts, the mitogenic effect of EGF requires activation of the IGF-1R by circulating ligands including IGF-I, IGF-II, or insulin [ 175 ].…”

Section: Egfr Regulates Aging-related Metabolic Activitymentioning

confidence: 99%

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Central Role of the EGF Receptor in Neurometabolic Aging

Siddiqui

Fang

et al. 2012

International Journal of Endocrinology

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A strong connection between neuronal and metabolic health has been revealed in recent years. It appears that both normal and pathophysiological aging, as well as neurodegenerative disorders, are all profoundly influenced by this “neurometabolic” interface, that is, communication between the brain and metabolic organs. An important aspect of this “neurometabolic” axis that needs to be investigated involves an elucidation of molecular factors that knit these two functional signaling domains, neuronal and metabolic, together. This paper attempts to identify and discuss a potential keystone signaling factor in this “neurometabolic” axis, that is, the epidermal growth factor receptor (EGFR). The EGFR has been previously demonstrated to act as a signaling nexus for many ligand signaling modalities and cellular stressors, for example, radiation and oxidative radicals, linked to aging and degeneration. The EGFR is expressed in a wide variety of cells/tissues that pertain to the coordinated regulation of neurometabolic activity. EGFR signaling has been highlighted directly or indirectly in a spectrum of neurometabolic conditions, for example, metabolic syndrome, diabetes, Alzheimer's disease, cancer, and cardiorespiratory function. Understanding the positioning of the EGFR within the neurometabolic domain will enhance our appreciation of the ability of this receptor system to underpin highly complex physiological paradigms such as aging and neurodegeneration.

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“…However, no previous study had examined this possibility under short-term conditions. The manner by which MMPs may be “beneficial” remains to be determined; however, scenarios include the possibility that MMPs may “activate” via their proteolytic action biological mediators of cardioprotection such as humoral factors, which would act in an autocrine and/or paracrine manner 36. One such possibility could be the cleavage of insulin-like growth factor or transforming growth factor-β1 by MMP-7.…”

Section: Discussionmentioning

confidence: 99%

Effects of Novel Semiselective Matrix Metalloproteinase Inhibitors on Ex Vivo Cardiac Structure-Function

Romero-Perez

Agrawal²,

Jacobsen³

et al. 2009

Journal of Cardiovascular Pharmacology

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The purpose of this study was to evaluate the ability of novel semiselective matrix metalloproteinase inhibitors (MMPI) to protect myocardial structure-function in the setting of ischemia-reperfusion injury. For this purpose, an isolated rat model of myocardial stunning and infarction was used. Isolated hearts were subjected to 20-30 minutes of global no-flow ischemia and 30-minute reperfusion. Myocardial performance was assessed as the product of the heart rate and left ventricular developed pressure (rate-pressure product, RPP). Coronary flow rates, ventricular weights, indicators of muscle (troponin I), and fibrillar collagen damage (collagen opalation) were measured. Four MMPI were tested: 2 non-hydroxamate, semiselective inhibitors (PY-2 and 1,2-HOPO-2) and 2 broad-spectrum inhibitors (PD166793 and CGS27023A). The non-hydroxamate, semiselective inhibitors were shown to be nontoxic in cocultures of cardiac cells. Results indicate that semiselective inhibitors (in particular 1,2-HOPO-2) yield improved cardiac performance (~23% higher RPP vs. controls) and coronary flow rates (~22%), reducing muscle (~25%) and fibrillar collagen damage (~60%). Evidence suggests the involvement of matrix metalloproteinase-2 in these actions. Interestingly, broad-spectrum inhibitors only show modest improvement (~8% higher RPP vs. controls) without affecting the other measured parameters. In conclusion, semiselective MMPI can act as cardioprotectors in isolated perfused rat hearts. Protection is observed in all structural components of the myocardium translating into improved contractile function. Based on these findings, non-hydroxamate, semiselective MMPI warrant further studies as to their ability to protect ischemic myocardium in the in vivo setting.

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Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Cited by 4 publications

References 40 publications

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Central Role of the EGF Receptor in Neurometabolic Aging

Effects of Novel Semiselective Matrix Metalloproteinase Inhibitors on Ex Vivo Cardiac Structure-Function

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Insulin-induced epidermal growth factor activation in vascular smooth muscle cells is ADAM-dependent

Cited by 4 publications

References 40 publications

Intracellular Transactivation of Epidermal Growth Factor Receptor byα1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Central Role of the EGF Receptor in Neurometabolic Aging

Effects of Novel Semiselective Matrix Metalloproteinase Inhibitors on Ex Vivo Cardiac Structure-Function

Contact Info

Product

Resources

About

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

Intracellular Transactivation of Epidermal Growth Factor Receptor byα_1A-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells