Stimulation of transient receptor potential M3 (TRPM3) channels increases interleukin-8 gene promoter activity involving AP-1 and extracellular signal-regulated protein kinase

Cytokine ◽  
2018 ◽  
Vol 103 ◽  
pp. 133-141 ◽  
Author(s):  
Sandra Rubil ◽  
Andrea Lesch ◽  
Naofumi Mukaida ◽  
Gerald Thiel
Keyword(s):  
Protein Kinase ◽  
Promoter Activity ◽  
Transient Receptor Potential ◽  
Gene Promoter ◽  
Receptor Potential ◽  
Interleukin 8 ◽  
Extracellular Signal ◽  
Transient Receptor ◽  
Stimulation Of

scholarly journals Activation of CaMKII and ERK1/2 contributes to the time-dependent potentiation of Ca2+ response elicited by repeated application of capsaicin in rat DRG neurons

2011 ◽  
Vol 300 (3) ◽  
pp. R644-R654 ◽  
Author(s):  
Xiulin Zhang ◽  
Stephanie L. Daugherty ◽  
William C. de Groat
Keyword(s):  
Protein Kinase ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Repeated Application ◽  
Drg Neurons ◽  
Intracellular Signaling Pathway ◽  
Short Intervals ◽  
Extracellular Signal ◽  
Transient Receptor

When capsaicin is applied repeatedly to dorsal root ganglion (DRG) neurons for brief periods (10–15 s) at short intervals (5–10 min), the evoked responses rapidly decline, a phenomenon termed tachyphylaxis. In addition to this phenomenon, the present study using Ca2+ imaging revealed that repeated application of capsaicin to rat dissociated DRG neurons at longer intervals (20–40 min) or during multiple applications at short intervals elicited an enhancement of the responses, termed potentiation. The potentiation occurred in 50–60% of the capsaicin-responsive cells, on average representing a 20- to 30% increase in the peak amplitude of the Ca2+ signal, and was maximal at a 40-min application interval. An analysis of the mechanisms underlying potentiation revealed that it was suppressed by block of Ca2+/calmodulin-dependent protein kinase II (CaMKII) with 5 μM KN-93 or block of the activation of extracellular signal-regulated kinase (ERK) 1/2 with 2 μM U-0126. Lowering the extracellular Ca2+ concentration from 2 to 1 mM or pretreatment with deltamethrin (1 μM), which blocks calcineurin and tachyphylaxis, enhanced potentiation. Potentiation was not affected by: 1) inhibition of protein kinase C or protein kinase A, 2) block of the three subtypes of neurokinin receptors, or 3) block of the trafficking of transient receptor potential V1 channel to the membrane. These results indicate that the potentiation is a slowly developing Ca2+-modulated process that is mediated by a complex intracellular signaling pathway involving activation of CaMKII and ERK1/2. Potentiation may be an important peripheral autosensitization mechanism that occurs independently of the pronociceptive effects of inflammatory mediators and neurotrophic factors.

scholarly journals Polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by differentially modulating STIM1 and STIM2

2012 ◽  
Vol 303 (3) ◽  
pp. C308-C317 ◽  
Author(s):  
Jaladanki N. Rao ◽  
Navneeta Rathor ◽  
Ran Zhuang ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Intestinal Epithelial Cell ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Intestinal Epithelial ◽  
Canonical Transient Receptor Potential ◽  
Pathological Conditions ◽  
Epithelial Restitution ◽  
Transient Receptor ◽  
Stimulation Of

Early epithelial restitution occurs as a consequence of intestinal epithelial cell (IEC) migration after wounding, and its defective regulation is implicated in various critical pathological conditions. Polyamines stimulate intestinal epithelial restitution, but their exact mechanism remains unclear. Canonical transient receptor potential-1 (TRPC1)-mediated Ca2+ signaling is crucial for stimulation of IEC migration after wounding, and induced translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane activates TRPC1-mediated Ca2+ influx and thus enhanced restitution. Here, we show that polyamines regulate intestinal epithelial restitution through TRPC1-mediated Ca2+ signaling by altering the ratio of STIM1 to STIM2. Increasing cellular polyamines by ectopic overexpression of the ornithine decarboxylase (ODC) gene stimulated STIM1 but inhibited STIM2 expression, whereas depletion of cellular polyamines by inhibiting ODC activity decreased STIM1 but increased STIM2 levels. Induced STIM1/TRPC1 association by increasing polyamines enhanced Ca2+ influx and stimulated epithelial restitution, while decreased formation of the STIM1/TRPC1 complex by polyamine depletion decreased Ca2+ influx and repressed cell migration. Induced STIM1/STIM2 heteromers by polyamine depletion or STIM2 overexpression suppressed STIM1 membrane translocation and inhibited Ca2+ influx and epithelial restitution. These results indicate that polyamines differentially modulate cellular STIM1 and STIM2 levels in IECs, in turn controlling TRPC1-mediated Ca2+ signaling and influencing cell migration after wounding.

scholarly journals Activation of TRPV1 channels leads to stimulation of NKCC1 cotransport in the lens

2018 ◽  
Vol 315 (6) ◽  
pp. C793-C802 ◽  
Author(s):  
Mohammad Shahidullah ◽  
Amritlal Mandal ◽  
Nicholas A. Delamere
Keyword(s):  
Ion Transport ◽  
Transient Receptor Potential ◽  
Ion Homeostasis ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Signaling Mechanism ◽  
Trpv1 Channels ◽  
Trpv1 Antagonist ◽  
Transient Receptor ◽  
Stimulation Of

Lens ion homeostasis is crucial in maintaining water content and, in turn, refractive index and transparency of the multicellular syncytium-like structure. New information is emerging on the regulation of ion transport in the lens by mechanisms that rely on transient receptor potential vanilloid (TRPV) ion channels. We found recently that TRPV1 activation leads to Ca2+/PKC-dependent ERK1/2 signaling. Here, we show that the TRPV1 agonist capsaicin (100 nM) and hyperosmotic solution (350 vs. 300 mosM) each caused an increase of bumetanide-inhibitable Rb uptake by intact porcine lenses and Na-K-2Cl cotransporter 1 (NKCC1) phosphorylation in the lens epithelium. The TRPV1 antagonist A889425 (1 µM) abolished the increases of Rb uptake and NKCC1 phosphorylation in response to hyperosmotic solution. Exposing lenses to hyperosmotic solution in the presence of MEK/ERK inhibitor U0126 (10 µM) or the with-no-lysine kinase (WNK) inhibitor WNK463 (1 µM) also prevented NKCC1 phosphorylation and the Rb uptake responses to hyperosmotic solution. WNK463 did not prevent the increase in ERK1/2 phosphorylation that occurs in response to capsaicin or hyperosmotic solution, suggesting that ERK1/2 activation occurs before WNK activation in the sequence of signaling events. Taken together, the evidence indicates that activation of TRPV1 is a critical early step in a signaling mechanism that responds to a hyperosmotic stimulus, possibly lens shrinkage. By activating ERK1/2 and WNK, TRPV1 activation leads to NKCC1 phosphorylation and stimulation of NKCC1-mediated ion transport.

Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor

2009 ◽  
Vol 297 (2) ◽  
pp. C360-C368 ◽  
Author(s):  
Elie Abed ◽  
Robert Moreau
Keyword(s):  
Growth Factor ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Platelet Derived Growth Factor ◽  
Human Osteoblast ◽  
Osteoblast Proliferation ◽  
Transient Receptor ◽  
And Migration ◽  
Stimulation Of ◽  
Proliferation And Migration

Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg2+) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg2+ and melastatin-like transient receptor potential 7 (TRPM7), known as Mg2+ channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg2+, enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg2+ concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg2+ influx, proliferation, and migration. Our results indicate that extracellular Mg2+ and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg2+ deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis.

Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents

2013 ◽  
Vol 304 (12) ◽  
pp. R1070-R1084 ◽  
Author(s):  
Arijit Roy ◽  
Fatemeh Derakhshan ◽  
Richard J. A. Wilson
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Carotid Body ◽  
Stress Responses ◽  
Transient Receptor Potential ◽  
Channel Blocker ◽  
Receptor Potential ◽  
Peak Response ◽  
Transient Receptor ◽  
Multiple Signaling

Consistent with a critical role in respiratory and autonomic stress responses, the carotid bodies are strongly excited by pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide implicated in stress responses throughout the sympathetic nervous system. PACAP excites isolated carotid body glomus cells via activation of PAC1 receptors, with one study suggesting PAC1-induced excitation is due entirely to protein kinase A (PKA)-mediated inhibition of TASK channels. However, in other systems, PAC1 is known to be coupled to multiple intracellular signaling pathways, including PKA, phospholipase C (PLC), phospholipase D (PLD), and protein kinase C (PKC), that trigger multiple downstream effectors including increased Ca2+ mobilization, inhibition of various K+ channels, and activation of nonselective cation channels. This study tests if non-PKA/TASK channel signaling helps mediate the stimulatory effects of PACAP on the carotid body. Using an ex vivo arterially perfused rat carotid body preparation, we show that PACAP-38 stimulates carotid sinus nerve activity in a biphasic manner (peak response, falling to plateau). PKA blocker H-89 only reduced the plateau response (∼41%), whereas the TASK-1-like K+ channel blocker/transient receptor potential vanilloid 1 channel agonist anandamide only inhibited the peak response (∼48%), suggesting involvement of additional pathways. The PLD blocker CAY10594 significantly inhibited both peak and plateau responses. The PLC blocker U73122 decimated both peak and plateau responses. Brefeldin A, a blocker of Epac (cAMP-activated guanine exchange factor, reported to link Gs-coupled receptors with PLC/PLD), also reduced both phases of the response, as did blocking signaling downstream of PLC/PLD with the PKC inhibitors chelerythrine chloride and GF109203X. Suggesting the involvement of non-TASK ion channels in the effects of PACAP, the A-type K+ channel blocker 4-aminopyridine, and the putative transient receptor potential channel (TRPC)/T-type calcium channel blocker SKF96365 each significantly inhibited the peak and steady-state responses. These data suggest the stimulatory effect of PACAP-38 on carotid body sensory activity is mediated through multiple signaling pathways: the PLC-PKC pathways predominates, with TRPC and/or T-type channel activation and Kv channel inactivation; only partial involvement is attributable to PKA and PLD activation.

scholarly journals Volatile Anesthetics Reduce Invasion of Colorectal Cancer Cells through Down-regulation of Matrix Metalloproteinase-9

2012 ◽  
Vol 117 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Björn Müller-Edenborn ◽  
Birgit Roth-Z'graggen ◽  
Kamila Bartnicka ◽  
Alain Borgeat ◽  
Alexandra Hoos ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Volatile Anesthetics ◽  
Interleukin 8 ◽  
Myristate Acetate ◽  
Kinase C ◽  
Extracellular Signal ◽  
Metalloproteinase 9 ◽  
Stimulation Of

Background Invasion of extracellular matrix is a hallmark of malignant tumors. Clamping maneuvers during cancer surgery reduce blood loss, but trigger reperfusion injury (RI). RI increases cancer recurrence in the reperfused organ through up-regulation of matrix metalloproteinase-9 (MMP-9). Interleukin-8 is an important cytokine in RI promoting accumulation of neutrophils, a major source of MMP-9. Volatile anesthetics were demonstrated to reduce RI. We hypothesized that these anesthetics might attenuate MMP-9 up-regulation and consequently tumor cell invasion in RI. Methods Isolated human neutrophils (n = 6) were preconditioned with sevoflurane or desflurane, followed by stimulation with interleukin-8, phorbol myristate acetate, or chemokine CXC-ligand 1 (CXCL1) to differentiate intracellular pathways. MMP-9 release and activity were quantified by enzyme-linked immunosorbent assay and zymography, respectively. CXC-receptor-2 (CXCR2) expression and phosphorylation of extracellular signal-regulated kinases 1/2 were assessed by flow cytometry. The impact of MMP-9 on the invasion of neutrophils and MC-38 colon cancer cells was assessed using Matrigel-coated filters (n = 6). Results Preconditioning reduced interleukin-8-induced MMP-9-release by 41% (±13, 5%, sevoflurane) and 40% (±13%, desflurane). This was also evident following stimulation of CXCR2 with CXCL1. No impact on phosphorylation of extracellular signal-regulated kinases 1/2 and MMP-9 release was observed with receptor-independent stimulation of protein kinase C with phorbol myristate acetate. Preconditioning reduced transmigration of neutrophils and MC-38 tumor cells to baseline levels. Discussion Volatile anesthetics impair neutrophil MMP-9 release and interfere with pathways downstream of CXCR2, but upstream of protein kinase C. Through down-regulation of MMP-9, volatile anesthetics decrease Matrigel breakdown and reduce subsequent migration of cancer cells in vitro.

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