Activation of protein kinase C by tyrosine phosphorylation in response to H
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Konishi, Hiroaki; Tanaka, Mikiya; Takemura, Yukie; Matsuzaki, Hidenori; Ono, Yoshitaka; Kikkawa, Ushio; Nishizuka, Yasutomi

doi:10.1073/pnas.94.21.11233

Cited by 584 publications

(481 citation statements)

References 36 publications

(35 reference statements)

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“…Furthermore, there is an interesting interactive and feed-forward relationship between PKC and ROS whereby PKC activation induces ROS production and ROS also can activate PKC pathways. Hydrogen peroxide activates PKC isoforms ␣, ␤, and ␥ (20), and the oxidative activation of PKC may enhance or facilitate the release of vasoconstrictor neurotransmitters, such as norepinephrine and ATP, from peripheral sympathetic nerves (11,29). Particularly, with the consideration of a high sympathetic outflow present in hypertension (2), such as in DOCA-salt hypertensive rats (39), ROS-activated PKC may result in elevated neurotransmitter release from nerve terminals innervating blood vessels and, accordingly, increase blood pressure.…”

Section: Discussionmentioning

confidence: 99%

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Dai

Chen²,

Kreulen³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Ϫ ⅐) production is elevated in sympathetic ganglion neurons and in the vasculature of hypertensive animals; however, it is not known what enzymatic pathway(s) are responsible for O 2 Ϫ ⅐ production. To determine the pathway(s) of O 2 Ϫ ⅐ production in sympathetic neurons, we examined the presence of mRNA of NADPH oxidase subunits in sympathetic ganglionic neurons and differentiated PC-12 cells. The mRNAs for NADPH oxidase subunits p47 phox , p22 phox , gp91 phox , and NOX1 were present in sympathetic neurons and PC-12 cells, whereas the NOX4 homologue was present in sympathetic neurons but not PC-12 cells. Freshly dissociated celiac ganglion neurons from normal rats and PC-12 cells produced O 2 Ϫ ⅐ when treated with the PKC activator PMA; O 2 Ϫ ⅐ production increased by 317% and 254%, respectively. The PMA-evoked increases were reduced by pretreatment with the NADPH oxidase inhibitor apocynin. These findings indicate that NADPH oxidase is the primary source of O 2 Ϫ ⅐ in sympathetic ganglion neurons. When celiac ganglia from hypertensive rats were incubated with apocynin, O 2 Ϫ ⅐ levels were reduced to the same levels as normotensive animals, indicating that NADPH oxidase activity accounted for the elevated O 2 Ϫ ⅐ levels in hypertensive animals. To test this latter finding, we compared NADPH oxidase activity in extracts of prevertebral sympathetic ganglia of DOCA-salt hypertensive rats and shamoperated rats. NADPH oxidase activities were 49.9% and 78.6% higher in sympathetic ganglia of DOCA rats compared with normotensive controls when using ␤-NADH and ␤-NADPH as substrates, respectively. Thus elevated O 2 Ϫ ⅐ levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons. sympathetic ganglia; phorbol ester; reduced nicotinamide adenine dinucleotide phosphate oxidase; hypertension; deoxycorticosterone acetate VASCULAR ENDOTHELIAL CELLS, smooth muscle cells, and fibroblasts generate reactive oxygen species (ROS), such as O 2 Ϫ ⅐ and H 2 O 2 . ROS play critical roles in both normal and pathophysiological states of vascular cells, including the modulation of redox-sensitive signaling pathways and gene expression, or in the pathophysiology of hypertension and atherosclerosis (16,22,26,36). Several models of hypertension are associated with an increase in vascular O 2 Ϫ ⅐ (41, 42), and this increased O 2 Ϫ ⅐ may quench the endogenous vasodilator nitric oxide (NO) to cause a loss of NO bioactivity in the vessel wall and impair the endothelium-dependent vasorelaxation, resulting in hypertension (26). ROS-mediated endothelial dysfunction in ANG II-infused rats (24) and in DOCA-salt hypertensive rats (42) can be reversed by antioxidant enzyme, endothelial NO synthase (34), or superoxide dismutase (26). ROS can also induce the expression of cardiovascular-related genes, such as those for adhesion molecules and vasoactive substances. For example, the cytokine interleukin 1 activates VCAM-1 gene expression through a mechanism that is repressed ϳ90% by the antioxidant...

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Section: Discussionmentioning

confidence: 99%

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Dai

Chen²,

Kreulen³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Tyrosine phosphorylation of PKCδ has been reported for responses of salivary gland cells in response to carbachol [44,45], COS-7 cells in response to H 2 O 2 [46,47], and, in addition, skeletal muscle cells in response to insulin [12]. Mouse, rat and human PKCδ contain 19, 21 and 20 tyrosine residues respectively.…”

Section: Mechanisms Of Activationmentioning

confidence: 97%

“…Tyrosine phosphorylation, while thought to be a relatively specific regulatory mechanism for PKCδ [48], may be a common regulatory mechanism for the entire family of PKC enzymes. No uniform pattern or consequence of PKCδ tyrosine phosphorylation can be extracted from the published literature, since the catalytic activity of tyrosine-phosphorylated PKCδ is variably described as decreased, increased, or even altered with regard to substrate specificity and cofactor requirements [45,46,[49][50][51]. In fact, the precise configuration of tyrosine residues phosphorylated on PKCδ depends upon the nature of the particular stimulus and dictates the functional properties of the enzyme.…”

Section: Mechanisms Of Activationmentioning

confidence: 99%

“…In current studies, we (unpublished) have found that PKCε is also tyrosine phosphorylated and activated in response to insulin. Src tyrosine kinase has been shown to be involved in insulin and other growth factor signaling in several cell types, including skeletal muscle [52][53][54][55][56][57][58][59][60][42][43][44][45][46][47][48][49]. Moreover, in the case of PKCs α and δ, insulin-induced tyrosine phosphorylation is apparently mediated by the Src family of tyrosine kinases, if not Src tyrosine kinase itself ( [31] and unpublished).…”

Section: Mechanisms Of Activationmentioning

confidence: 99%

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Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Sampson

Cooper

2006

Molecular Genetics and Metabolism

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Recent studies implicate specific PKC isoforms in the insulin-signaling cascade. Insulin activates PKCsα, βII, δ and ζ in several cell types. In addition, as will be documented in this review, certain members of the PKC family may also be activated and act upstream of PI3 and MAP kinases. Each of these isoforms has been shown one way or another either to mimic or to modify insulin-stimulated effects in one or all of the insulin-responsive tissues. Moreover, each of the isoforms has been shown to be activated by insulin stimulation or conditions important for effective insulin stimulation. Studies attempting to demonstrate a definitive role for any of the isoforms have been performed on different cells, ranging from appropriate model systems for skeletal muscle, liver and fat, such as primary cultures, and cell lines and even in vivo studies, including transgenic mice with selective deletion of specific PKC isoforms. In addition, studies have been done on certain expression systems such as CHO or HEK293 cells, which are far removed from the tissues themselves and serve mainly as vessels for potential protein-protein interactions. Thus, a clear picture for many of the isoforms remains elusive in spite of over two decades of intensive research. The recent intrusion of transgenic and precise molecular biology technologies into the research armamentarium has opened a wide range of additional possibilities for direct involvement of individual isoforms in the insulin signaling cascade. As we hope to discuss within the context of this review, whereas many of the long soughtafter answers to specific questions are not yet clear, major advances have been made in our understanding of precise roles for individual PKC isoforms in mediation of insulin effects. In this review, in which we shall focus our attention on isoforms in the conventional and novel categories, a clear case will be made to show that these isoforms are not only expressed but are importantly involved in regulation of insulin metabolic effects.

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“…Both PMA and Thy had little effect on the level of h, i/l, m, u, and z isoforms. Next, we examined PKC isoforms that could be phosphorylated on their tyrosine residues when cells were treated with IFN-g since tyrosine phosphorylation could be considered as activation of PKCs [7,16]. Upon IFN-g treatment, tyrosine phosphorylation of a and 1 was increased while that of b and d was not changed (Fig.…”

mentioning

confidence: 99%

Identification of protein kinase C isoforms involved in interferon-gamma-induced expression of inducible nitric oxide synthase in murine BV2 microglia

Kang

Yang

Jou

et al. 2001

Neuroscience Letters

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Activation of protein kinase C by tyrosine phosphorylation in response to H ₂ O ₂

Cited by 584 publications

References 36 publications

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Identification of protein kinase C isoforms involved in interferon-gamma-induced expression of inducible nitric oxide synthase in murine BV2 microglia

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Activation of protein kinase C by tyrosine phosphorylation in response to H 2 O 2

Cited by 584 publications

References 36 publications

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase

Specific protein kinase C isoforms as transducers and modulators of insulin signaling

Identification of protein kinase C isoforms involved in interferon-gamma-induced expression of inducible nitric oxide synthase in murine BV2 microglia

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Product

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Activation of protein kinase C by tyrosine phosphorylation in response to H ₂ O ₂