Synthesis of kininogen and degradation of bradykinin by PC12 cells

Dendorfer, Andreas; Wellhöner, Peter; Braun, Andreas; Roscher, Adelbert A.; Dominiak, Peter

doi:10.1038/sj.bjp.0701547

Cited by 12 publications

(8 citation statements)

References 40 publications

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“…The non-bioluminescence MDA-MB-231 indicate the presence of at least one of these receptors (B1R) [47, 50], suggesting they are likely to be present in the bioluminescent line as well. Cancer cell lines vary in their production of HMWK [50–52]. Importantly, in the current study we demonstrate that this basal release of HMWK increase rapidly (within 1 h) after exposure to all three tested NPs.…”

Section: Discussionsupporting

confidence: 61%

Neuropeptide-induced modulation of carcinogenesis in a metastatic breast cancer cell line (MDA-MB-231LUC+)

Gutiérrez

Boada

2018

Cancer Cell Int

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BackgroundMetastatic cancer to bone is well-known to produce extreme pain. It has been suggested that the magnitude of this perceived pain is associated with disease progression and poor prognosis. These data suggest a potential cross-talk between cancer cells and nociceptors that contribute not only to pain, but also to cancer aggressiveness although the underlying mechanisms are yet to be stablished.MethodsThe in vitro dose dependent effect of neuropeptides (NPs) (substance P [SP], calcitonin gene-related peptide and neurokinin A [NKA]) and/or its combination, on the migration and invasion of MDA-MB-231LUC+ were assessed by wound healing and collagen-based cell invasion assays, respectively. The effect of NPs on the expression of its receptors (SP [NK1] and neurokinin A receptors [NK2], CALCRL and RAMP1) and kininogen (high-molecular-weight kininogen) release to the cell culture supernatant of MDA-MB-231LUC+, were measured using western-blot analysis and an ELISA assay, respectively. Statistical significance was tested using one-way ANOVA, repeated measures ANOVA, or the paired t-test. Post-hoc testing was performed with correction for multiple comparisons as appropriate.ResultsOur data show that NPs strongly modify the chemokinetic capabilities of a cellular line commonly used as a model of metastatic cancer to bone (MDA-MB-231LUC+) and increased the expression of their receptors (NK1R, NK2R, RAMP1, and CALCRL) on these cells. Finally, we demonstrate that NPs also trigger the acute release of HMWK (Bradykinin precursor) by MDA-MB-231LUC+, a molecule with both tumorigenic and pro-nociceptive activity.ConclusionsBased on these observations we conclude that NPs exposure modulates this breast cancer cellular line aggressiveness by increasing its ability to migrate and invade new tissues. Furthermore, these results also support the pro nociceptive and cancer promoter role of the peripheral nervous system, during the initial stages of the disease.

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Section: Discussionsupporting

confidence: 61%

Neuropeptide-induced modulation of carcinogenesis in a metastatic breast cancer cell line (MDA-MB-231LUC+)

Gutiérrez

Boada

2018

Cancer Cell Int

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“…In vivo BK is produced by proteolytic cleavage of a precursor at the surface of neurons and endothelium. The cleavage is mediated by protease activity that is linked to the blood coagulation system and is activated by injury (29,30). In the human brain, BK B 2 receptors are localized to neurons, the target cell type in AD (31), while in the periphery, these receptors are found in nociceptive neurons as well as vascular and connective tissue infrastructure (reviewed in refs 13, 14, and 19).…”

Section: Discussionmentioning

confidence: 99%

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediatingtauprotein Ser phosphorylation

Jong¹,

Ford²,

Seehra³

et al. 2003

FASEB j.

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Increased Ser phosphorylation of tau microtubule-associated protein in the brain is an early feature of Alzheimer's disease (AD) that precedes progression of the disease to frank neuronal disruption. We demonstrate that bradykinin (BK) B2 receptor activation leads to selective Ser phosphorylation of tau in skin fibroblasts from persons who have or will develop AD due to Presenilin 1 mutations or Trisomy 21, but not in skin fibroblasts from normal individuals at any age. The increased signal transduction in AD fibroblasts that culminates in tau Ser phosphorylation reflects modification of the G protein-coupled BK B2 receptors themselves. Both the BK B2 receptor modification and BK-mediated tau Ser phosphorylation are dependent on activation of protein kinase C and can be detected in fibroblasts from persons with Trisomy 21 two decades before the characteristic onset of AD. This dysregulated signaling cascade in AD may thus be expressed throughout life as an aberrant pathway in peripheral tissues more accessible than brain for molecular analysis. The sites of greatest BK B2 receptor expression in brain overlap with those areas displaying the earliest pathology in the course of AD, suggesting that BK receptor pathway dysfunction may be a molecular signature yielding information about the pathogenesis of AD.

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“…Kkin‐F ACTAGACATGACATCAGTG, H‐R TGCATGCAACCAGCCATGC, TL‐R GCCCTTGTACTCACATGAG, plasma‐KalliR CTGTAATGCTCTCTTCATG, and plasma‐kalliF CCTTGTTCGCTACAGTT (23).…”

Section: Methodsmentioning

confidence: 99%

Kinin‐B2 receptor expression and activity during differentiation of embryonic rat neurospheres

et al. 2008

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Neural progenitor cells were isolated from rat fetal telencephalon and proliferate as neurospheres in the presence of EGF, FGF-2, and heparin. In the absence of these growth factors, neurospheres differentiate into neurons, astrocytes, and oligodendrocytes. Using an embryonal carcinoma cell line as in vitro differentiation model, we have already demonstrated the presence of an autocrine loop system between kinin-B2 receptor activity and secretion of its ligand bradykinin (BK) as prerequisites for final neuronal differentiation (Martins et al., J Biol Chem 2005; 280: 19576-19586). The aim of this study was to verify the activity of the kallikrein-kinin system (KKS) during neural progenitor cell differentiation. Immunofluorescence studies and flow cytometry analysis revealed increases in glial fibrillary acidic protein and b-3 tubulin expression and decrease in the number of nestin-positive cells along neurospheres differentiation, indicating the transition of neural progenitor cells to astrocytes and neurons. Kinin-B2 receptor expression and activity, secretion of BK into the medium, and presence of highmolecular weight kininogen suggest the participation of the KKS in neurosphere differentiation. Functional kinin-B2 receptors and BK secretion indicate an autocrine loop during neurosphere differentiation to neurons, astrocytes, and oligodendrocytes, reflecting events occurring during early brain development. ' 2008 International Society for Analytical CytologyKey terms kinin-B2 receptor; neural differentiation; neurosphere; kallikrein-kinin system BRADYKININ (BK), kallidin, des-Arg 9 -BK, and des-Arg 9 -kallidin are the biological active peptides of the kallikrein-kinin system (KKS). BK and kallidin as ligands of Gprotein-coupled kinin-B2 receptors (B2BKR) are generated upon proteolytic cleavage of high-or low-molecular weight kininogen (HMWK or LMWK) by plasma-or tissue-kallikrein serine protease, respectively. Carboxy-terminal arginines are removed from these biological active peptides by carboxypeptidases M or N to originate the kinin-B1 receptor (B1BKR) agonists des-Arg 9 -BK and des-Arg 9 -kallidin (Fig. 1). Stimulation of the B2BKR by its agonists results in the activation of phospholipase C-b (PLC-b), generating diacyl glycerol and inositol 1,4,5-triphosphate (IP 3 ) and resulting in release of Ca 21 from intracellular IP 3 -sensitive stores. Furthermore, BK mediates the activation of endothelial nitric oxide synthase (1) and stimulates the phospholipase A2 activity (2). B2BKR also activates proteins with tyrosine kinase activity (3), and the receptor can directly interact with neuronal and endothelial nitric oxide synthetase (nNOS and eNOS), resulting in NO production (4). Both B1BKR and B2BKR are coupled to G aq and G ai proteins (5,6) and triggered the same signaling pathways, but differ in their expression pattern and intensities of receptorinduced calcium responses and receptor-desensitization rates (7).B2BKR is constitutively expressed and broadly distributed throughout the tissues, and B1BK...

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Synthesis of kininogen and degradation of bradykinin by PC12 cells

Cited by 12 publications

References 40 publications

Neuropeptide-induced modulation of carcinogenesis in a metastatic breast cancer cell line (MDA-MB-231LUC+)

Neuropeptide-induced modulation of carcinogenesis in a metastatic breast cancer cell line (MDA-MB-231LUC+)

Alzheimer's disease skin fibroblasts selectively express a bradykinin signaling pathway mediatingtauprotein Ser phosphorylation

Kinin‐B2 receptor expression and activity during differentiation of embryonic rat neurospheres

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