Mechanisms of MAPK activation by bradykinin  in vascular smooth muscle cells

Velarde, Victoria; Ullian, Michael E.; Morinelli, Thomas A.; Mayfield, Ronald K.; Jaffa, Ayad A.

doi:10.1152/ajpcell.1999.277.2.c253

Cited by 92 publications

(63 citation statements)

References 38 publications

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“…Moreover, the activation of ERK1/2 by BK has been demonstrated in various cells lines: A431, mesangial, and vascular smooth muscle cells (20,25,50). It is noteworthy that the proliferative effect of BK has been essentially demonstrated in quiescent mesangial cells with high concentrations of BK.…”

Section: Discussionmentioning

confidence: 96%

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Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation

Cellier

Mage

Duchêne

et al. 2003

American Journal of Physiology-Renal Physiology

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Several experimental data report both mitogenic and antimitogenic effects of bradykinin (BK). To conciliate these apparent opposite effects, we hypothesized that, depending on cell context activation, BK could reduce the mitogenic effect of growth factors. Therefore, in the present study we assessed the existence of possible negative cross talk between BK and potential pathogenic growth factors in freshly isolated rat glomeruli (IG). Next, we determined whether this cross talk could be pharmacologically recruited during angiotensin-converting enzyme (ACE) inhibition in the diabetic rat. In IG from normal rats, BK, via activation of the B2 kinin receptor (B2R), causes a transient stimulation of ERK1/2 phosphorylation, whereas it inhibits ERK1/2 phosphorylation induced by IGF-1, PDGF-BB, VEGF, or basic FGF. The reduction of growth factor-induced ERK1/2 phosphorylation is abolished by an inhibitor of tyrosine phosphatase. In glomeruli from diabetic rats, hyperglycemia increased the phosphorylation level of ERK-1/2 as well as oxidative stress. The reversal of these events by ACE inhibition is mediated via B2R activation. These observations are consistent with a potential therapeutic role of BK and B2R during glomerulosclerosis.

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Section: Discussionmentioning

confidence: 96%

“…The profibrogenic effects of BK are associated with the phosphorylation of ERK1/2, which is a prerequisite for the activation of this MAPK (18). Finally, the activation of ERK1/2 by BK has been demonstrated in various cells lines: A431, mesangial, and vascular smooth muscle cells (20,25,50).…”

mentioning

confidence: 99%

Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation

Cellier

Mage

Duchêne

et al. 2003

American Journal of Physiology-Renal Physiology

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“…Indeed, under normal physiological conditions, BK is a potent stimulator of nitric oxide release from renal and endothelial cells, which result in vasodilatation because of effects on underlying vascular smooth muscle cells (40,41). However, when the endothelium is denuded or dysfunctional, as is observed in disease states such as hypertension or diabetes, BK can act directly on mesangial and vascular smooth muscle cells (VSMCs) to induce contraction and to activate multiple signaling pathways, in a manner similar to those activated by vasoconstrictors, ultimately resulting in changes in cell proliferation and increased matrix deposition (42)(43)(44)(45)(46). Thus BK can protect from vascular disease associated with diabetes when there is an intact endothelium, but could aggravate vascular disease when endothelium is damaged.…”

Section: Fig 2 Continuous Variable Correlation Plots Between Pk Andmentioning

confidence: 99%

Plasma Prekallikrein

et al. 2003

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The relevance and significance of the plasma kallikrein/ kinin system as a risk factor for the development of vascular complications in diabetic patients was explored in a cross-sectional study. We measured the circulating levels of plasma prekallikrein (PK) activity, factor XII, and high؊molecular weight kininogen in the plasma of 636 type 1 diabetic patients from the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications Study cohort. The findings demonstrated that type 1 diabetic patients with blood pressure >140/90 mmHg have increased PK levels compared with type 1 diabetic patients with blood pressure <140/90 (1.53 ؎ 0.07 vs. 1.27 ؎ 0.02 units/ml; P < 0.0001). Regression analysis also determined that plasma PK levels positively and significantly correlated with diastolic (DBP) and systolic blood pressures (SBP) as continuous variables (r ‫؍‬ 0.17 and 0.18, respectively; P < 0.0001). In multivariate regression analysis, the semipartial r 2 value for PK was 2.93% for SBP and 2.92% for DBP (P < 0.0001). A positive correlation between plasma PK levels and the urinary albumin excretion rate (AER) was also observed (r ‫؍‬ 0.16, P < 0.0001). In categorical analysis, patients with macroalbuminuria had a significantly higher level of plasma PK than normoalbuminuric patients (1.45 ؎ 0.08 vs. 1.27 ؎ 0.02 units/ml; P < 0.01), whereas microalbuminuric patients had an intermediate PK value (1.38 ؎ 0.05 units/ml; P ‫؍‬ NS). Among patients in the microalbuminuric subgroup, we observed a positive and independent correlation between PK and AER in univariate and multivariate regression analysis (r ‫؍‬ 0.27, P < 0.03; n ‫؍‬ 63). We concluded that in type 1 diabetes, 1) PK levels are elevated in association with increased blood pressure;2) PK levels are independently correlated with AER and are categorically elevated in patients with macroalbuminuria; and 3) although the positive correlation between PK and AER within the subgroups of patients with microalbuminuria suggest that PK could be a marker for progressive nephropathy, longitudinal studies will be necessary to address this issue.

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“…This suggests a two-way interaction/activation between two signaling systems. The cytoskeletal proteins ankyrin and adducin (25,26) and cytoskeleton-related kinases such as focal adhesion kinase are good candidates for mediating the link between a conformational change in the sodium pump to its neighboring proteins in the membrane (27). Ouabain-induced signaling is intriguing considering that recently many researchers have isolated a variety of substances commonly termed endogenous digitalis-like factors from plasma or urine of healthy as well as hypertensive individuals (28 -31).…”

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confidence: 99%

Ouabain-induced Signaling and Vascular Smooth Muscle Cell Proliferation

Aydemir-Koksoy¹,

Abramowitz²,

Allen³

2001

Journal of Biological Chemistry

158

138

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The hypothesis of this study is that the sodium pump complex acts as an intracellular signal-transducing molecule in canine vascular smooth muscle cells through its interaction with other membrane and cytoskeletal proteins. We have demonstrated that 1 nM ouabain induced transactivation of the epidermal growth factor receptor (EGFR), resulting in increased proliferation and bromodeoxyuridine (BrdUrd) uptake. Immunoprecipitation and Western blotting showed that the EGFR and Src were phosphorylated within 5 min of 10 ؊9 M ouabain stimulation. Both ouabain-induced DNA synthesis (BrdUrd uptake) and MAPK42/44 phosphorylation were inhibited by the Src inhibitor PP2, the EGFR kinase inhibitor AG1478, the tyrosine kinase inhibitor genistein, and the MEK1 inhibitor PD98059. Ouabain concentrations higher than 1 nM had little or no stimulating effect on proliferation or BrdUrd uptake but did minimally activate ERK1/2. Thus, low concentrations of ouabain, which do not inhibit the sodium pump sufficiently to perturb the resting cellular ionic milieu, initiate a transactivational signaling cascade leading to vascular smooth muscle cell proliferation.The role of the sodium pump as a regulator of intracellular ionic balance has been well documented. However, research in this area has recently shown that this protein complex has the potential to function in ways that apparently do not involve these well documented ionic shifts. For example, Peng et al. (1) reported that the sodium pump complex can function as a molecular signal transducer in rat cardiac myocytes. Kometiani et al. (2) further showed that 10 Ϫ4 -10 Ϫ5 M (10 -100 M) ouabain activated cardiac myocyte hypertrophy and MAPK42/ 44 1 phosphorylation. Recently many growth factor signaling pathways have been shown to involve EGFR transactivation in VSMCs (3, 4) as was also shown earlier in cardiac myocytes (5). In this paper we describe the ability of low concentrations of ouabain (0.1-1.0 nM) to induce proliferation of cultured canine vascular smooth muscle cells via a signaling cascade involving Src, EGFR, and MAPK42/44. The isolation of ouabain-like substances from the plasma and urine samples of both healthy and hypertensive individuals (6), as well as a variety of animal tissues, has suggested potentially important paradigms for these agents in the modulation of cell function through interaction with the sodium pump. MATERIALS AND METHODSAll chemicals were obtained from Sigma. Ouabain (o-3125 and o-5754) from Sigma and ouabain (75640) from Fluka were used. All kinase inhibitors were from Calbiochem. Antibodies for Src, phosphotyrosine (4G10, monoclonal), and EGFR were from Upstate Biotechnology Inc. (Waltham, MA). The antibody for MAPK42/44 (E10, monoclonal) was from Cell Signaling Technology Inc. (New England BioLabs, Beverly, MA). Anti-active EGFR antibody was purchased from Transduction Laboratories.Vascular Smooth Muscle Cell Culture-Vascular smooth muscle cells were isolated from the saphenous veins of mongrel dogs by a two-step enzymatic digestion procedure as...

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Mechanisms of MAPK activation by bradykinin in vascular smooth muscle cells

Cited by 92 publications

References 38 publications

Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation

Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation

Plasma Prekallikrein

Ouabain-induced Signaling and Vascular Smooth Muscle Cell Proliferation

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