Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways

Jong, Yuh-Jiin I.; Dalemar, L. R.; Wilhelm, B.; Baenziger, Nancy Lewis

doi:10.1016/0162-3109(96)00075-6

Cited by 3 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The signaling actions of BKB1R in response to desArg 9 ‐BK or desArg 10 ‐kallidin are very similar to those of BKB2R with respect to the activation of phosphatidyl inositol (PI) turnover, arachidonate (ARA) release, Ca 2+ mobilization, and the induction of the immediate early gene, c‐fos. (Cahill et al, 1988; Menke et al, 1994; Jong et al, 1996; Zhou et al, 1999; Schaeffer et al, 2001). Like BK, desArg 9 ‐BK also induces protein formation and cell division (Goldstein and Wall, 1984; Beny et al, 1987; Churchill and Ward, 1987; Vianna and Calixto, 1998; Prat et al, 1999).…”

Section: Receptor Signalingmentioning

confidence: 99%

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Prado

Taylor

Zhou

et al. 2002

Journal Cellular Physiology

157

124

View full text Add to dashboard Cite

Bradykinin (BK) is a potent short-lived effector belonging to a class of peptides known as kinins. It participates in inflammatory and vascular regulation and processes including angioedema, tissue permeability, vascular dilation, and smooth muscle contraction. BK exerts its biological effects through the activation of the bradykinin B2 receptor (BKB2R) which is G-protein-coupled and is generally constitutively expressed. Upon binding, the receptor is activated and transduces signal cascades which have become paradigms for the actions of the Gai and Gaq G-protein subunits. Following activation the receptor is then desensitized, endocytosed, and resensitized. The bradykinin B1 (BKB1R) is a closely related receptor. It is activated by desArg 10 -kallidin or desArg 9 -BK, metabolites of kallidin and BK, respectively. This receptor is induced following tissue injury or after treatment with bacterial endotoxins such as lipopolysacharide or cytokines such as interleukin-1 or tumor necrosis factor-a. In this review we will summarize the BKB2R and BKB1R mediated signal transduction pathways. We will then emphasize the relevance of key residues and domains of the intracellular regions of the BKB2R as they relate to modulating its function (signal transduction) and selfmaintenance (desensitization, endocytosis, and resensitization). We will examine the features of the BKB1R gene promoter and its mRNA as these operate in the expression and self-maintenance of this inducible receptor. This communication will not cover areas discussed in earlier reviews pertaining to the actions of peptide analogs. For these we refer you to earlier reviews

show abstract

Section: Receptor Signalingmentioning

confidence: 99%

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Prado

Taylor

Zhou

et al. 2002

Journal Cellular Physiology

157

124

View full text Add to dashboard Cite

show abstract

“…A common element of this molecular profile appearing in all presenilin and non-presenilin-based genetic forms of AD risk we tested is the initial BK-induced BKB2R Tyr phosphorylation itself, positioned early in the BKB2R signaling cascade [8], [12], [13], [14]. Beyond this initial step, our present studies now reveal multiple points of divergence in the downstream signaling cascades in AD cells of differing genetic origins.…”

Section: Discussionmentioning

confidence: 55%

“…We previously found that activation of PKC by 25 nM phorbol myristate acetate (PMA) or by treatment with 250 nM BK prompted modulation of the BKB2R in AD skin fibroblasts (Table 1), detected by monoclonal anti-BKB2R antibodies recognizing the modulated receptors that reflect enhanced activity of a Tyr phosphorylation pathway in the AD cells [8], [12]. Only trace, non-PKC-dependent levels of the phosphorylated receptor occur in skin fibroblasts of normal controls.…”

Section: Resultsmentioning

confidence: 99%

“…Normal control and PS-1 (M146L) AD human skin fibroblasts were stimulated for 0–30 min with BK concentrations of 25 or 250 nM, which respectively target the I (intermediate) and L (low) affinity phosphorylated BKB2R forms we previously characterized in AD fibroblasts [12], [13], [39], [40]. Cell lysates collected in 1% SDS were immunoblotted after SDS-PAGE using phospho-epitope specific antibodies to quantitate activity of MAPK modules (p38, ERK and JNK).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously defined exaggerated signal transduction in AD patients' skin fibroblasts in response to the inflammatory neuropeptide bradykinin (BK). Levels of this nonapeptide mediator generated via a proteolytic cascade increase under environmental insults such as stroke, head trauma injury, and pain [8], [11], to initiate signaling pathways via G-protein-coupled receptors [12]. In a PKC-dependent process the BK B2 subtype receptor (BKB2R) is modulated to forms that reflect activity of a Tyr phosphorylation pathway [13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Profiling Reveals Diversity of Stress Signal Transduction Cascades in Highly Penetrant Alzheimer's Disease Human Skin Fibroblasts

et al. 2009

View full text Add to dashboard Cite

The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD) as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R) inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival pathway in normal fibroblasts lost in PS-1 M146L fibroblasts. Complex molecular profiles of signaling dysfunction in the most putatively straightforward human cellular models of AD suggest that risk ascertainment and therapeutic interventions in AD as a whole will likely demand complex solutions.

show abstract

Pharmacological Characterization Of Bradykinin B₁ and B₂ Receptors In IMR‐90 and INT‐407 Human Cell Lines Using A Microphysiometer

Bentley

Jarrott

2001

Clin Exp Pharma Physio

View full text Add to dashboard Cite

1. In the present study, we used a microphysiometer to measure bradykinin-induced acidification responses in IMR-90, a human lung fibroblast cell line, and INT-407, a human colonic epithelial cell line. Furthermore, we investigated the effect of 24 h exposure of transforming growth factor (TGF)-alpha on the bradykinin response in INT-407 cells. 2. Bradykinin (0.1-100 nmol/L) was potent in producing acidification responses in IMR-90 cells (pEC50 8.79+/-0.13; Hill slope 0.96+/-0.04) and INT-407 cells (pEC50 8.90+/-0.04; Hill slope 1.00+/-0.07). These responses were competitively antagonized by the bradykinin B2 receptor antagonist icatibant in both IMR-90 cells (apparent pKB = 8.54+/-0.15; Hill slope = 1.09+/-0.13 and 1.66+/-0.26 in the absence and presence of 10 nmol/L icatibant, respectively) and INT-407 cells (pKB = 8.12+/-0.07 (3, 10 and 30 nmol/L icatibant); Hill slope = 1.06+/-0.04). However, the bradykinin B1 receptor antagonist des-Arg9Leu8-bradykinin (3 micromol/L) had no effect on the bradykinin responses. 3. The non-peptide bradykinin B2 receptor antagonist FR173657 selectively antagonized bradykinin-induced acidification responses in INT-407 cells in a competitive manner (pKB = 8.76+/-0.10; Hill slope = 0.92+/-0.05) at lower concentrations (1 and 3 nmol/L) but in an insurmountable manner at higher concentrations (10 nmol/L; Hill slope = 1.04+/-0.09). This compound, at concentrations of 10 and 100 nmol/L (Hill slope = 1.38+/-0.15), also proved to be an insurmountable antagonist in IMR-90 cells. 4. The bradykinin B1 receptor selective agonist Lys0des-Arg10-bradykinin (0.1 nmol/L to 0.1 micromol/L) failed to produce acidification responses in IMR-90 cells, even after 24 h pre-incubation with bacterial lipopolysaccharide (0.1 microg/mL). 5. A 24 h pre-incubation of INT-407 cells with TGF-alpha (1, 10 and 100 ng/mL) caused a significant concentration-dependent decrease in maximal bradykinin response without affecting the pEC50. 6. In addition to this study being the first to use a microphysiometer to characterize bradykinin B2 receptors in cultured IMR-90 human lung fibroblast cells and INT-407 human colonic epithelial cells, we also showed that pre-incubation of INT-407 cells with TGF-alpha caused a significant decrease in maximal acidification response mediated by bradykinin B2 receptors.

show abstract

Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways

Cited by 3 publications

References 15 publications

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Molecular Profiling Reveals Diversity of Stress Signal Transduction Cascades in Highly Penetrant Alzheimer's Disease Human Skin Fibroblasts

Pharmacological Characterization Of Bradykinin B₁ and B₂ Receptors In IMR‐90 and INT‐407 Human Cell Lines Using A Microphysiometer

Contact Info

Product

Resources

About

Human lung fibroblasts express multiple means for enhanced activity of bradykinin receptor pathways

Cited by 3 publications

References 15 publications

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Mechanisms regulating the expression, self‐maintenance, and signaling‐function of the bradykinin B2 and B1 receptors

Molecular Profiling Reveals Diversity of Stress Signal Transduction Cascades in Highly Penetrant Alzheimer's Disease Human Skin Fibroblasts

Pharmacological Characterization Of Bradykinin B1 and B2 Receptors In IMR‐90 and INT‐407 Human Cell Lines Using A Microphysiometer

Contact Info

Product

Resources

About

Pharmacological Characterization Of Bradykinin B₁ and B₂ Receptors In IMR‐90 and INT‐407 Human Cell Lines Using A Microphysiometer