scholarly journals Angiotensin II regulation of neuromodulation: downstream signaling mechanism from activation of mitogen-activated protein kinase.

1996 ◽  
Vol 135 (6) ◽  
pp. 1609-1617 ◽  
Author(s):  
D Lu ◽  
H Yang ◽  
M K Raizada
Keyword(s):  
Angiotensin Ii ◽  
Map Kinase ◽  
Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Signaling Mechanism ◽  
Downstream Signaling ◽  
Neuronal Soma ◽  
Mitogen Activated Protein

Angiotensin II (Ang II) stimulates expression of tyrosine hydroxylase and norepinephrine transporter genes in brain neurons; however, the signal-transduction mechanism is not clearly defined. This study was conducted to determine the involvement of the mitogen-activated protein (MAP) kinase signaling pathway in Ang II stimulation of these genes. MAP kinase was localized in the perinuclear region of the neuronal soma. Ang II caused activation of MAP kinase and its subsequent translocation from the cytoplasmic to nuclear compartment, both effects being mediated by AT1 receptor subtype. Ang II also stimulated SRE- and AP1-binding activities and fos gene expression and its translocation in a MAP kinase-dependent process. These observations are the first demonstration of a downstream signaling pathway involving MAP kinase in Ang II-mediated neuromodulation in noradrenergic neurons.

Angiotensin II regulates phosphorylation of translation elongation factor-2 in cardiac myocytes

2001 ◽  
Vol 281 (1) ◽  
pp. H161-H167 ◽  
Author(s):  
Allen D. Everett ◽  
Tamara D. Stoops ◽  
Angus C. Nairn ◽  
David Brautigan
Keyword(s):  
Protein Synthesis ◽  
Angiotensin Ii ◽  
Cardiac Myocytes ◽  
Elongation Factor ◽  
Protein Translation ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Elongation Factor 2 ◽  
Mitogen Activated Protein ◽  
20 Nm

Increased protein synthesis is the cardinal feature of cardiac hypertrophy. We have studied angiotensin II (ANG II)-dependent regulation of eukaryotic elongation factor-2 (eEF-2), an essential component of protein translation required for polypeptide elongation, in rat neonatal cardiac myocytes. eEF2 is fully active in its dephosphorylated state and is inhibited following phosphorylation by eEF2 kinase. ANG II treatment (10−10–10−7 M) for 30 min produced an AT1 receptor-specific and concentration- and time-dependent reduction in the phosphorylation of eEF-2. Protein phosphatase 2A (PP2A) inhibitors okadaic acid and fostriecin, but not the PP2B inhibitor FK506, attenuated ANG II-dependent dephosphorylation of eEF-2. ANG II activated mitogen-activated protein kinase, (MAPK) within 10 min of treatment, and blockade of MAPK activation with PD-98059 (1–20 nM) inhibited eEF-2 dephosphorylation. The effect of ANG II on eEF-2 dephosphorylation was also blocked by LY-29004 (1–20 nM), suggesting a role for phosphoinositide 3-kinase, but the mammalian target rapamycin inhibitor rapamycin (10–100 nM) had no effect. Together these results suggest that the ANG II-dependent increase in protein synthesis includes activation of eEF-2 via dephosphorylation by PP2A by a process that involves both PI3K and MAPK.

Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases

2007 ◽  
Vol 293 (4) ◽  
pp. H2403-H2408 ◽  
Author(s):  
Guo-Xing Zhang ◽  
Yukiko Nagai ◽  
Toshitaka Nakagawa ◽  
Hiroshi Miyanaka ◽  
Yoshihide Fujisawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Map Kinase ◽  
Map Kinases ◽  
No Synthase ◽  
Dependent Manner ◽  
Ang Ii ◽  
No Donor ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation

Angiotensin II (ANG II) is a powerful activator of mitogen-activated protein (MAP) kinase cascades in cardiovascular tissues through a redox-sensitive mechanism. Nitric oxide (NO) is considered to antagonize the vasoconstrictive and proarteriosclerotic actions of ANG II. However, the role of endogenous NO in ANG II-induced redox-sensitive signal transduction is not yet clear. In this study using catheterized, conscious rats, we found that acute intravenous administration of NG-nitro-l-arginine methyl ester (l-NAME; 5 mg/kg) enhanced phosphorylation of aortic MAP kinases extracellular signal regulated kinase (ERK) 1/2 and p38, which were suppressed only partially by a superoxide dismutase mimetic (Tempol), whereas ANG II-induced MAP kinase phosphorylation was markedly suppressed by Tempol. FK409, a NO donor, had little effect on vascular MAP kinase phosphorylation. On the other hand, acute exposure to a vasoconstrictor dose of ANG II (200 ng·kg−1·min−1 iv) failed to enhance phosphorylation of aortic MAP kinases in the chronically l-NAME-treated rats, whereas the vasoconstrictor effect of ANG II was not affected by l-NAME treatment. Furthermore, three different inhibitors of NO synthase suppressed, in a dose-dependent manner, ANG II-induced MAP kinase phosphorylation in rat vascular smooth muscle cells, which was closely linked to superoxide generation in cells. These results indicate the involvement of endogenous NO synthase in ANG II-induced signaling pathways, leading to activation of MAP kinase, and that NO may have dual effects on the vascular MAP kinase activation associated with redox sensitivity.

scholarly journals Role of the JIP4 Scaffold Protein in the Regulation of Mitogen-Activated Protein Kinase Signaling Pathways

2005 ◽  
Vol 25 (7) ◽  
pp. 2733-2743 ◽  
Author(s):  
Nyaya Kelkar ◽  
Claire L. Standen ◽  
Roger J. Davis
Keyword(s):  
Map Kinase ◽  
Signaling Pathway ◽  
Scaffold Protein ◽  
P38 Map Kinase ◽  
Scaffold Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Signaling ◽  
Interacting Protein ◽  
Jnk Signaling ◽  
Mitogen Activated Protein

ABSTRACT The c-Jun NH2-terminal kinase (JNK)-interacting protein (JIP) group of scaffold proteins (JIP1, JIP2, and JIP3) can interact with components of the JNK signaling pathway and potently activate JNK. Here we describe the identification of a fourth member of the JIP family. The primary sequence of JIP4 is most closely related to that of JIP3. Like other members of the JIP family of scaffold proteins, JIP4 binds JNK and also the light chain of the microtubule motor protein kinesin-1. However, the function of JIP4 appears to be markedly different from other JIP proteins. Specifically, JIP4 does not activate JNK signaling. In contrast, JIP4 serves as an activator of the p38 mitogen-activated protein (MAP) kinase pathway by a mechanism that requires the MAP kinase kinases MKK3 and MKK6. The JIP4 scaffold protein therefore appears to be a new component of the p38 MAP kinase signaling pathway.

scholarly journals Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase

1993 ◽  
Vol 90 (23) ◽  
pp. 10952-10956 ◽  
Author(s):  
R H Chen ◽  
C Abate ◽  
J Blenis
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
S6 Kinase ◽  
Downstream Signaling ◽  
C Terminus ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

Phosphorylation of the C terminus of c-Fos has been implicated in serum response element-mediated repression of c-fos transcription after its induction by serum growth factors. The growth-regulated enzymes responsible for this phosphorylation in early G1 phase of the cell cycle and the sites of phosphorylation have not been identified. We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. The phosphorylation sites identified for RSK (Ser-362) and MAP kinase (Ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling.

scholarly journals The Milk Thistle (Silybum marianum) Compound Silibinin Inhibits Cardiomyogenesis of Embryonic Stem Cells by Interfering with Angiotensin II Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Enas Hussein Ali ◽  
Fatemeh Sharifpanah ◽  
Amer Taha ◽  
Suk Ying Tsang ◽  
Maria Wartenberg ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Es Cells ◽  
Embryonic Stem ◽  
Embryoid Bodies ◽  
Mitogen Activated Protein Kinase ◽  
Milk Thistle ◽  
Ang Ii ◽  
Silybum Marianum ◽  
Angiotensin Ii Signaling ◽  
Mitogen Activated Protein

The milk thistle (Silybum marianum (L.) Gaertn.) compound silibinin may be an inhibitor of the angiotensin II type 1 (AT1) receptor which is expressed in differentiating embryonic stem (ES) cells and is involved in the regulation of cardiomyogenesis. In the present study, it was demonstrated that silibinin treatment decreased the number of spontaneously contracting cardiac foci and cardiac cell areas differentiated from ES cells as well as contraction frequency and frequency of calcium (Ca2+) spiking. In contrast, angiotensin II (Ang II) treatment stimulated cardiomyogenesis as well as contraction and Ca2+ spiking frequency, which were abolished in the presence of silibinin. Intracellular Ca2+ transients elicited by Ang II in rat smooth muscle cells were not impaired upon silibinin treatment, excluding the possibility that the compound acted on the AT1 receptor. Ang II treatment activated extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways in embryoid bodies which were abolished upon silibinin pretreatment. In summary, our data suggest that silibinin inhibits cardiomyogenesis of ES cells by interfering with Ang II signaling downstream of the AT1 receptor.

scholarly journals Angiotensin II Activates Mitogen-Activated Protein Kinase Via Protein Kinase C and Ras/Raf-1 Kinase in Bovine Adrenal Glomerulosa Cells

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1801-1809 ◽  
Author(s):  
Ying Tian ◽  
Roger D. Smith ◽  
Tamas Balla ◽  
Kevin J. Catt
Keyword(s):  
Protein Kinase C ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Time Course ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Mapk Activation ◽  
Kinase C ◽  
Mitogen Activated Protein ◽  
Glomerulosa Cells

Abstract Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10–50 pm. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

Chronic Angiotensin II Augments Integrin-Dependent Cell Functions Via PKC and Map-Kinase Activation in Rat Vsmcs

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 707-707
Author(s):  
Kai Kappert ◽  
Florian Blaschke ◽  
Gunther Schmidt ◽  
Eckart Fleck ◽  
Ronald E Law ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Map Kinase ◽  
Critical Role ◽  
Collagen I ◽  
Mitogen Activated Protein Kinase ◽  
Chronic Hypertension ◽  
Ang Ii ◽  
Kinase Activation ◽  
Cell Functions

P78 The activation of local and systemic renin-angiotensin-system is directly and indirectly involved in the mechanisms of vascular remodeling during chronic hypertension. The following study investigated the effect of chronic angiotensin II (AII) admininstration on cell- matrix interaction of VSMCs in vitro. Adhesion to vitronectin (VN) and collagen I (ColI) as well as migration of rat vascular smooth muscle cells (VSMCs) were significantly augmented by chronic treatment with AII for 48 hours and 72 hours. These changes were not due to an increase of the integrins on the cells surface known to be capable in binding vitronectin and collagen I: alpha1, alpha5, beta1 and beta5, as demonstrated by flow cytometry. Also the phosporylation of the focal adhesion kinase (FAK), known to play an important role in adhesion and spreading processes, was not affected after chronic stimulation with Ang II. Downregulation of PKC activity by phorbol-myristate acetate (PMA, 0.1μmol/L), or treatment with the PKC inhibitor calphostin C before treatment with AII significantly reduced the effect of AII on adhesion to VN and ColI (each p<0.05) and also inhibited the effect on VSMC migration (p<0.01). Inhibition of MAP-kinase activation with PD 98059 before treatment with AII demonstrated comparable effects. PD 98059 significantly reduced the increase in adhesion on both, VN and ColI and diminished the effect on PDGF-directed migration of rVSMCs. Theses data indicate that regulation of these functional alterations in integrin-dependent cellular behaviour after chronic AII treatment involved protein kinase C (PKC) and mitogen-activated protein kinase (MAPK)-activation. These data demonstrate that Ang II plays a critical role in augmenting cellular functions in VSMCs, which are important molecular events for the development of vascular hyperplasia .

ERK activation contributes to regulation of spontaneous contractile tone via superoxide anion in isolated rat aorta of angiotensin II-induced hypertension

2007 ◽  
Vol 292 (6) ◽  
pp. H2997-H3005 ◽  
Author(s):  
Lili Ding ◽  
Alexander Chapman ◽  
Ryan Boyd ◽  
Hui Di Wang
Keyword(s):  
Angiotensin Ii ◽  
Signaling Pathway ◽  
Superoxide Anion ◽  
Rat Aorta ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Ang Ii ◽  
Superoxide Generation ◽  
Spontaneous Tone

Arteries from hypertensive animals and humans have increased spontaneous tone. Increased superoxide anion (superoxide) contributes to elevated blood pressure (BP) and spontaneous tone in hypertension. The association between the extracellular signaling-regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK) signaling pathway and generation of superoxide and spontaneous tone in isolated aorta was studied in angiotensin II (ANG II)-infused hypertensive (HT) rats. Systolic BP, phosphorylation of ERK, aortic superoxide formation, and aortic spontaneous tone were compared in sham normotensive and HT rats. Infusion of ANG II (0.5 mg·kg−1·day−1 for 6 days) significantly elevated the systolic BP ( P < 0.01). The phosphorylation of ERK1/2 vs. total ERK1/2 in thoracic aorta was enhanced, and superoxide was increased in the HT vs. the sham group ( P < 0.01). Spontaneous tone developed in the HT group, but not in the normotensive group. MAPK/ERK1/2 (MEK1/2)-ERK1/2 signaling pathway inhibitors, PD-98059 (10 μmol/l), and U-0126 (10 μmol/l), significantly reduced the phosphorylation of ERK1/2, superoxide generation ( P < 0.01), and spontaneous tone ( P < 0.01) in HT. These findings suggest that ANG II infusion induces the production of superoxide and spontaneous tone and that both are dependent on ERK-MAPK activation. In endothelium-denuded aorta, however, MEK1/2 inhibitors did not inhibit the spontaneous tone, even though they significantly reduced superoxide generation similar to endothelium-intact aorta. These data suggest that inhibition of ERK1/2 signaling pathway, via PD-98059 or U-0126, may regulate spontaneous tone in an endothelium-dependent manner. In conclusion, these findings support the importance of the ERK1/2 signaling pathway in modulating vascular oxidative stress and subsequently mediating spontaneous tone in HT.

scholarly journals NAMPT/SIRT1 Attenuate Ang II-Induced Vascular Remodeling and Vulnerability to Hypertension by Inhibiting the ROS/MAPK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Lei Zhou ◽  
Sheng Zhang ◽  
Enkhbat Bolor-Erdene ◽  
Lingwei Wang ◽  
Ding Tian ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Mapk Pathway ◽  
Sirtuin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Ang Ii ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Aortic Endothelial Cells ◽  
Mitogen Activated Protein

Hypertension is characterized by endothelial dysfunction, vascular remodeling, and rearrangement of the extracellular matrix. Besides, the pathogenesis of hypertension is closely related to excess generation of reactive oxygen species (ROS). Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis that influences the activity of NAD-dependent enzymes, such as sirtuins, which possess NAD-dependent protein deacetylase activity and cleave NAD during the deacetylation cycle. Recently, NAMPT has been shown to play a crucial role in various diseases associated with oxidative stress. However, the function and regulation of NAMPT in hypertension have not been extensively explored. In the present study, we identified NAMPT as a crucial regulator of hypertension, because NAMPT expression was significantly downregulated in both patients with hypertension and experimental animals. NAMPT knockout (NAMPT+/-) mice exhibited a significantly higher blood pressure and ROS levels after stimulation with angiotensin II (Ang II) than wild-type mice, and the administration of recombinant human NAMPT (rhNAMPT) reversed this effect. In vivo, overexpression of NAMPT protected against angiotensin II- (Ang II-) induced hypertension by inhibiting ROS production via sirtuin 1 in mouse aortic endothelial cells (MAECs) and mouse aortic vascular smooth muscle cells (MOVAs). In turn, NAMPT alleviated the ROS-induced mitogen-activated protein kinase (MAPK) pathway. In conclusion, NAMPT might be a novel biomarker and a therapeutic target in hypertension.

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