Involvement of Growth Factor Receptor and Nonreceptor Protein Tyrosine Kinases in Endothelin-1 and Angiotensin II-Induced Signaling Pathways in the Cardiovascular System

Vardatsikos, George; Srivastava, Ashok K.

doi:10.1007/978-1-4419-7130-2_23

Cited by 2 publications

(2 citation statements)

References 165 publications

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“…Abnormal migration, growth, and proliferation of VSMCs are believed to be key events, which contribute to the structural remodeling of blood vessels and have been attributed to the pathogenesis of vascular diseases (Daniel & Sedding, ; Gonzalez‐Navarro et al, ; Ho et al, ; Kockx & Knaapen, ; Li, Hashim, & Anandsrivastava, ). A potential role of vasoactive peptides and growth factors in inducing proliferation, hypertrophy, migration, and differentiation of VSMCs has been demonstrated (Bayes‐Genis, Conover, & Schwartz, ; Bouallegue, Bou daou, & Srivastava, ; Cho et al, ; Vardatsikos, ). Earlier, we have shown that the transactivation of the insulin‐like growth factor 1 (IGF‐1) receptor is critical to induce the mitogenic and hypertrophic responses of two key vasoactive peptides, angiotensin II (Ang‐II) and endothelin‐1 (ET‐1; Bouallegue, Vardatsikos, & Srivastava, ).…”

Section: Introductionmentioning

confidence: 99%

Protein kinase B/AKT mediates insulin‐like growth factor 1‐induced phosphorylation and nuclear export of histone deacetylase 5 via NADPH oxidase 4 activation in vascular smooth muscle cells

Pietruczuk

Jain

Simo‐Cheyou

et al. 2019

Journal Cellular Physiology

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Insulin‐like growth factor 1 (IGF‐1) mediates the generation of reactive oxygen species (ROS) and the activation of growth promoting signaling pathways. Histone deacetylases (HDACs) regulate gene transcription by deacetylating lysine residues in histone and nonhistone proteins and a heightened HDAC activation, notably of HDAC5, is associated with vascular disorders, such as atherosclerosis. Although the contribution of IGF‐1 in these pathologies is well documented, its role in HDAC phosphorylation and activation remains unexplored. Here, we examined the effect of IGF‐1 on HDAC5 phosphorylation in vascular smooth muscle cells (VSMCs) and identified the signaling pathways involved in controlling HDAC5 phosphorylation and nuclear export. Treatment of A10 VSMCs with IGF‐1 enhanced HDAC5 phosphorylation. Blockade of the IGF‐1 receptor tyrosine kinase (TK) activity with the specific pharmacological inhibitor, AG1024, significantly inhibited IGF‐1‐induced HDAC5 phosphorylation, whereas the epidermal growth factor receptor (EGFR) TK antagonist, AG1478, had no effect. Inhibition of the mitogen‐activated protein kinase pathway with U0126, SP600125, or SB203580, did not affect HDAC5 phosphorylation, whereas two inhibitors of the phosphoinositide 3‐kinase (PI3K)/AKT pathways, wortmannin and SC66, almost completely attenuated IGF‐1‐induced responses as confirmed by immunoblotting of phospho‐HDAC5 and by small interfering RNA (siRNA)‐induced AKT silencing. Moreover, the NAD(P)H oxidase (Nox) inhibitor, diphenyleneiodonium (DPI), and Nox4 siRNA, attenuated IGF‐1‐induced phosphorylation of HDAC5 and AKT. The HDAC5 phosphorylation resulted in its nuclear export, which was reversed by SC66 and DPI. Our results indicate that IGF‐1‐induced phosphorylation and nuclear export of HDAC5 involve Nox4‐dependent ROS generation and PI3K/AKT signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Protein kinase B/AKT mediates insulin‐like growth factor 1‐induced phosphorylation and nuclear export of histone deacetylase 5 via NADPH oxidase 4 activation in vascular smooth muscle cells

Pietruczuk

Jain

Simo‐Cheyou

et al. 2019

Journal Cellular Physiology

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“…Aberrant proliferation, migration, and growth of vascular smooth muscle cells (VSMC) are believed to be key events in vascular remodelling and contribute to the pathogenesis of vascular abnormalities such as atherosclerosis, hypertension, and intimal thickening [Jackson and Schwartz, ; Vardatsikos and Srivastava, ]. The involvement of growth factors and vasoactive peptides such as endothelin‐1 (ET‐1) and angiotensin‐II (Ang‐II) in these processes has been well documented in the past decades.…”

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confidence: 99%

Early Growth Response Protein‐1 Expression by Insulin‐Like Growth Factor‐1 Requires ROS‐Dependent Activation of ERK1/2 and PKB Pathways in Vascular Smooth Muscle Cells

Youreva

Srivastava

2015

J of Cellular Biochemistry

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Early growth response protein-1 (Egr-1) is a transcription factor that plays an important role in the regulation of several genes implicated in the pathogenesis of cardiovascular disease (CVD) such as atherosclerosis. Insulin-like growth factor-1 (IGF-1), a potent mitogen, is believed to contribute to the development of CVD through the hyperactivation of mitogenic and growth promoting pathways, including the MAPK and PKB pathways, as well as regulation of multiple transcription factors. Reactive oxygen species (ROS) have been shown to mediate the effects of IGF-1 and are believed to contribute to the pathogenesis of vascular abnormalities. We have previously shown that IGF-1 induces the expression of Egr-1 in vascular smooth muscle cells (VSMC); however, the signaling pathways involved in this process remain unexplored. Therefore, we have investigated the involvement of MAPK, PKB, and ROS in IGF-1-induced Egr-1 expression in VSMC. Treatment of VSMC with IGF-1 enhanced Egr-1 protein levels in a time and dose-dependent fashion and PD98059 and SP600125, two selective inhibitors of ERK1/2 and JNK, respectively, significantly decreased IGF-1-induced increase in Egr-1 expression in these cells. In addition, blockade of PI3-K/PKB pathways by Wortmannin/SC-66 respectively, also attenuated IGF-1-induced Egr-1 protein as well as mRNA expression. Diphenyleneiodonium (DPI), an NAD(P)H oxidase inhibitor, blocked the Egr-1 expression in response to IGF-1. In summary, these data demonstrate that ROS-dependent activation of ERK1/2/JNK, PI3-K/PKB signaling events play a critical role in IGF-1 induced expression of Egr-1 in VSMC.

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Involvement of Growth Factor Receptor and Nonreceptor Protein Tyrosine Kinases in Endothelin-1 and Angiotensin II-Induced Signaling Pathways in the Cardiovascular System

Cited by 2 publications

References 165 publications

Protein kinase B/AKT mediates insulin‐like growth factor 1‐induced phosphorylation and nuclear export of histone deacetylase 5 via NADPH oxidase 4 activation in vascular smooth muscle cells

Protein kinase B/AKT mediates insulin‐like growth factor 1‐induced phosphorylation and nuclear export of histone deacetylase 5 via NADPH oxidase 4 activation in vascular smooth muscle cells

Early Growth Response Protein‐1 Expression by Insulin‐Like Growth Factor‐1 Requires ROS‐Dependent Activation of ERK1/2 and PKB Pathways in Vascular Smooth Muscle Cells

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