Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated endothelium promotes inflammation

Ngo, My-Linh; Mahdi, Fakhri; Kolte, Dhaval; Shariat‐Madar, Zia

doi:10.1186/1476-9255-6-3

Cited by 35 publications

(30 citation statements)

References 41 publications

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“…Moreover, inhibition of tyrosine phosphatase with sodium orthovanadate abolished AT 2 R-stimulated plasma prekallikrein activation and bradykinin release. Because plasma prekallikrein activation is an indirect measure of PRCP activity (18,25) and PRCP is known to have several tyrosine phosphorylation sites, our data suggest that AT 2 R-stimulated PRCPdependent plasma prekallikrein activation is mediated at least in part via SHP-1.…”

Section: Discussionmentioning

confidence: 77%

“…For kallikrein activity, we followed the methods established by Ngo et al (18) and Shariat-Madar et al (24). Cells seeded in 96-well plates were washed three times with HEPES-NaHCO 3 buffer containing 137 mM NaCl, 3 mM KCl, 10 M CaCl2, 1 mM MgCl2, 12 mM NaHCO3, 5.5 mM dextrose, 0.1% gelatin, and 14.7 mM HEPES (pH 7.1).…”

Section: Methodsmentioning

confidence: 99%

“…Dysfunction of PRCP is associated with adverse cardiovascular events such as hypertension and inflammation (18). In recent years PRCP-dependent plasma prekallikrein activation on endothelial cells (ECs) has received much attention.…”

mentioning

confidence: 99%

“…When the complex of highmolecular-weight kininogen (HMWK) and plasma prekallikrein binds to the endothelial membrane, PRCP converts plasma prekallikrein to kallikrein, which then cleaves HMWK, generating bradykinin, which leads to NO and prostacyclin formation as well as vasodilatation, probably by activating constitutive kinin B 2 and inducible B 1 receptors (15,24,25). Overexpression of PRCP in cultured Chinese hamster ovary cells and ECs enhanced plasma prekallikrein activation and release of kinins and NO, and these effects can be blocked by a small interfering RNA (siRNA) to PRCP (18,26,37). These data confirm the role of PRCP-dependent plasma prekallikrein activation in bradykinin release.…”

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confidence: 99%

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Angiotensin II type 2 receptor-stimulated activation of plasma prekallikrein and bradykinin release: role of SHP-1

Zhu

Carretero

Wang

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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XP. Angiotensin II type 2 receptor-stimulated activation of plasma prekallikrein and bradykinin release: role of SHP-1. Am J Physiol Heart Circ Physiol 302: H2553-H2559, 2012. First published April 20, 2012 doi:10.1152/ajpheart.01157.2011.-ANG II type 2 receptors (AT2R) elicit cardioprotective effects in part by stimulating the release of kinins; however, the mechanism(s) responsible have not been fully explored. We demonstrated previously that overexpression of AT2R increased expression of prolylcarboxypeptidase (PRCP; a plasma prekallikrein activator) and release of bradykinin by mouse coronary artery endothelial cells (ECs). In the present study we hypothesized that the AT2R-stimulated increase in PRCP is mediated by the tyrosine phosphatase SHP-1, which in turn activates the PRCP-dependent prekallikrein-kallikrein pathway and releases bradykinin. We found that activation of AT2R using the specific agonist CGP42112A increased SHP-1 activity in ECs, which was blocked by the AT2R antagonist PD123319. Activation of AT2R also enhanced conversion of plasma prekallikrein to kallikrein, and this effect was blunted by a small interfering RNA (siRNA) to SHP-1 and abolished by the tyrosine phosphatase inhibitor sodium orthovanadate. Treating cells with a siRNA to PRCP also blunted AT2R-stimulated prekallikrein activation and bradykinin release. Furthermore, blocking plasma kallikrein with soybean trypsin inhibitor (SBTI) abolished AT2R-stimulated bradykinin release. These findings support our hypothesis that stimulation of AT2R activates a PRCP-dependent plasma prekallikrein pathway, releasing bradykinin. Activation of SHP-1 may also play an important role in AT2R-induced PRCP activation.prolylcarboxypeptidase; plasma kallikrein-kinin system ANGIOTENSIN II (ANG II) is classically considered a vasoconstrictor and pro-growth molecule acting via the ANG II type 1 receptor (AT 1 R). Although the role of AT 2 R remains controversial, they are generally thought to be mutually antagonistic, with AT 2 R opposing the actions of AT 1 R (6, 14, 21). Some of the beneficial effects of AT 2 R are mediated by bradykinin/ nitric oxide (NO) (5, 10), and overexpression of AT 2 R in the vasculature reportedly stimulated the kinin system, causing dilatation (31). Likewise cardiac AT 2 R overexpression attenuated fibrosis induced by ANG II or myocardial infarction, apparently acting via a kinin/NO-dependent mechanism (3, 7). We have demonstrated that the cardioprotective effects of AT 1 R antagonists are mediated in part by activation of AT 2 R and kinins, since they were diminished in AT 2 R or kinin receptors knock out mice and kinin-deficient rats or by blocking the AT 2 R or kinin receptors (11, 34 -36). However, the precise mechanism(s) by which AT 2 R mediates kinin release is not yet known.Prolylcarboxypeptidase (PRCP) is a serine carboxypeptidase that cleaves a variety of COOH-terminal amino acids adjacent to proline and has been linked to hypertension and preeclampsia (1, 32) as well as obesity (23). Dysfunction of PRCP is associ...

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Section: Discussionmentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Angiotensin II type 2 receptor-stimulated activation of plasma prekallikrein and bradykinin release: role of SHP-1

Zhu

Carretero

Wang

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…On the contrary, incubation of HPAEC with HK and PK led to robust BK production (21). In the present study, LC/MS analysis of HK and a mixture of HK and PK were performed to determine proteolytic digests of HK on cultured HPAEC.…”

Section: High Molecular Weight Kininogen (Hk) Induces An Increase In mentioning

confidence: 99%

High Molecular Weight Kininogen Activates B2 Receptor Signaling Pathway in Human Vascular Endothelial Cells

Kolte

Osman

Yang

et al. 2011

Journal of Biological Chemistry

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The nonenzymatic cofactor high molecular weight kininogen (HK) is a precursor of bradykinin (BK). The production of BK from HK by plasma kallikrein has been implicated in the pathogenesis of inflammation and vascular injury. However, the functional role of HK in the absence of prekallikrein (PK), the proenzyme of plasma kallikrein, on vascular endothelial cells is not fully defined. In addition, no clinical abnormality is seen in PKdeficient patients. Therefore, an investigation into the effect of HK, in the absence of PK, on human pulmonary artery endothe- The plasma kallikrein-kinin system (KKS) 2 consists of three proenzymes; factor XII (FXII, Hageman factor), prekallikrein (PK, Fletcher factor), and factor XI (FXI, plasma thromboplastin antecedent) as well as one cofactor; high molecular weight kininogen (HK, Fitzgerald factor). KKS is involved in the regulation of hemodynamics, inflammation, complement activation, angiogenesis, thrombosis, and fibrinolysis. Basically, all these proposed roles represent a range of overlapping effects that contribute to various extents toward vasodilation and healing. Therefore, the plasma KKS can be considered to have a spectrum of physiological effects, ranging at one extreme from a hemostatic state of vasodilation and promotion of smooth blood flow, all the way to a prothrombotic state. It is conceivable to suggest that other mechanisms proposed about respiratory, retinal, and renal systems can fit into this spectrum of physiological effects (1-3). There is accumulating evidence suggesting that when the plasma KKS is activated, the results are a sequential release of proteolytic enzymes and vasoactive peptides, generation of both angiogenic and anti-angiogenic molecules, stabilization of thrombus, and an increase in protease inhibitor activity in blood (4 -7). The activation of HK-PK complex on endothelial cells triggers vasodilation through smooth muscle relaxation, inhibits platelet aggregation, and induces proinflammatory responses. Of note, the direct assembly of HK, PK, and FXII on vascular smooth muscle cells (VSMC) also results in the activation of PK to kallikrein (8). The induction of these physiological reactions is caused by the release of the vasoactive peptide bradykinin (BK) from HK by kallikrein. Bradykinin B 2 receptor activation by BK mediates the activation of endothelial nitric-oxide synthase (eNOS) and phospholipase A 2 (PLA 2 ) leading to production of nitric oxide (NO) and prostacylin (PGI 2 ). Evidence suggests that BK phosphorylates p44/42 mitogen-activated protein kinase in VMSC, which is blocked by BK antagonist HOE-140 (8).Besides having a direct effect on blood vessels, the HK-PK complex has also been shown to mediate the effects of other pro-inflammatory molecules. Recent study suggests that the inhibitors of both BK and factor XII activity protect from mast cell-induced effects not only in patients but also in genetically engineered mouse models. The authors proposed that this class of inhibitors could be useful to treat allergic diseases (9)....

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The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

Rhaleb

Yang

Carretero

2011

Comprehensive Physiology

107

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Autocrine, paracrine, endocrine, and neuroendocrine hormonal systems help regulate cardiovascular and renal function. Any change in the balance among these systems may result in hypertension and target organ damage, whether the cause is genetic, environmental or a combination of the two. Endocrine and neuroendocrine vasopressor hormones such as the renin-angiotensin system (RAS), aldosterone, and catecholamines are important for regulation of blood pressure and pathogenesis of hypertension and target organ damage. While the role of vasodepressor autacoids such as kinins is not as well defined, there is increasing evidence that they are not only critical to blood pressure and renal function but may also oppose remodeling of the cardiovascular system. Here we will primarily be concerned with kinins, which are oligopeptides containing the aminoacid sequence of bradykinin. They are generated from precursors known as kininogens by enzymes such as tissue (glandular) and plasma kallikrein. Some of the effects of kinins are mediated via autacoids such as eicosanoids, nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), and/or tissue plasminogen activator (†PA). Kinins help protect against cardiac ischemia and play an important part in preconditioning as well as the cardiovascular and renal protective effects of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor blockers (ARB). But the role of kinins in the pathogenesis of hypertension remains controversial. A study of Utah families revealed that a dominant kallikrein gene expressed as high urinary kallikrein excretion was associated with a decreased risk of essential hypertension. Moreover, researchers have identified a restriction fragment length polymorphism (RFLP) that distinguishes the kallikrein gene family found in one strain of spontaneously hypertensive rats (SHR) from a homologous gene in normotensive Brown Norway rats, and in recombinant inbred substrains derived from these SHR and Brown Norway rats this RFLP cosegregated with an increase in blood pressure. However, humans, rats and mice with a deficiency in one or more components of the kallikrein-kinin-system (KKS) or chronic KKS blockade do not have hypertension. In the kidney, kinins are essential for proper regulation of papillary blood flow and water and sodium excretion. B2-KO mice appear to be more sensitive to the hypertensinogenic effect of salt. Kinins are involved in the acute antihypertensive effects of ACE inhibitors but not their chronic effects (save for mineralocorticoidsalt-induced hypertension). Kinins appear to play a role in the pathogenesis of inflammatory diseases such as arthritis and skin inflammation; they act on innate immunity as mediators of inflammation by promoting maturation of dendritic cells, which activate the body’s adaptive immune system and thereby stimulate mechanisms that promote inflammation. On the other hand, kinins acting via NO contribute to the vascular protective effect of ACE inhibitors during neointima formation. In myocardial i...

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Upregulation of prolylcarboxypeptidase (PRCP) in lipopolysaccharide (LPS) treated endothelium promotes inflammation

Cited by 35 publications

References 41 publications

Angiotensin II type 2 receptor-stimulated activation of plasma prekallikrein and bradykinin release: role of SHP-1

Angiotensin II type 2 receptor-stimulated activation of plasma prekallikrein and bradykinin release: role of SHP-1

High Molecular Weight Kininogen Activates B2 Receptor Signaling Pathway in Human Vascular Endothelial Cells

The Kallikrein‐Kinin System as a Regulator of Cardiovascular and Renal Function

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