Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the heart, insulin-like growth factor-1 (IGF-1) is a pro-hypertrophic and anti-apoptotic peptide. In cultured rat cardiomyocytes, IGF-1 induced a fast and transient increase in Ca(2+)(i) levels apparent both in the nucleus and cytosol, releasing this ion from intracellular stores through an inositol 1,4,5-trisphosphate (IP(3))-dependent signaling pathway. Intracellular IP(3) levels increased after IGF-1 stimulation in both the presence and absence of extracellular Ca(2+). A different spatial distribution of IP(3) receptor isoforms in cardiomyocytes was found. Ryanodine did not prevent the IGF-1-induced increase of Ca(2+)(i) levels but inhibited the basal and spontaneous Ca(2+)(i) oscillations observed when cardiac myocytes were incubated in Ca(2+)-containing resting media. Spatial analysis of fluorescence images of IGF-1-stimulated cardiomyocytes incubated in Ca(2+)-containing resting media showed an early increase in Ca(2+)(i), initially localized in the nucleus. Calcium imaging suggested that part of the Ca(2+) released by stimulation with IGF-1 was initially contained in the perinuclear region. The IGF-1-induced increase on Ca(2+)(i) levels was prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, thapsigargin, xestospongin C, 2-aminoethoxy diphenyl borate, U-73122, pertussis toxin, and betaARKct (a peptide inhibitor of Gbetagamma signaling). Pertussis toxin also prevented the IGF-1-dependent IP(3) mass increase. Genistein treatment largely decreased the IGF-1-induced changes in both Ca(2+)(i) and IP(3). LY29402 (but not PD98059) also prevented the IGF-1-dependent Ca(2+)(i) increase. Both pertussis toxin and U73122 prevented the IGF-1-dependent induction of both ERKs and protein kinase B. We conclude that IGF-1 increases Ca(2+)(i) levels in cultured cardiac myocytes through a Gbetagamma subunit of a pertussis toxin-sensitive G protein-PI3K-phospholipase C signaling pathway that involves participation of IP(3).
 ...
PMID:Insulin-like growth factor-1 induces an inositol 1,4,5-trisphosphate-dependent increase in nuclear and cytosolic calcium in cultured rat cardiac myocytes. 1466 May 53

The increased resistance of the glomerulus as a result of contractile dysfunction of mesangial cells (MCs) is associated with reduction of glomerular filtration rate and development of glomerulosclerosis. Evidences show MCs contraction changes with intracellular Ca(2+) concentration ([Ca(2+)](i)). Here, we explore the mechanism of angiotensin II (AngII)-induced Ca(2+) oscillations and MCs contraction. Primary MCs from 3-month-old and 28-month-old rats were used for detection of Ca(2+) oscillations and MC planar area with confocal microscopy. AngII could induce typical Ca(2+) oscillations and contraction of MCs. This process was abolished by thapsigargin, 2-aminoethoxydiphenyl borate, or 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine, and partially inhibited by ryanodine, but could not be inhibited in the absence of extracellular Ca(2+). Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate (InsP(3)) receptors displayed a strong colocalization, which may contribute to the amplification of Ca(2+) response. MLC(20) phosphorylation and MC planar area were associated with AngII-induced Ca(2+) oscillations. The frequency of Ca(2+) oscillations was dependent on the AngII concentration and correlated with the MCs' contractive extent, which could be attenuated by KN-93. The amplitude reduction of oscillations correlated with the decrease in aging-related contraction. In conclusion, [Ca(2+)](i) response of MCs to AngII is characterized by repetitive spikes through the following repetitive cycles: Ca(2+) release by phospholipase C -InsP(3) pathway, Ca(2+) amplification by Ca(2+)-activated RyRs and Ca(2+) reuptake by the endoplasmic reticulum. MCs contraction can be modulated by oscillations not only in an AngII-induced frequency-dependent mode but also in an aging-related, amplitude-dependent mode.
 ...
PMID:Essential role of Ca2+ release channels in angiotensin II-induced Ca2+ oscillations and mesangial cell contraction. 1672 87

Hypoxia-induced mitogenic factor (HIMF), also known as "found in inflammatory zone 1" (FIZZ1) or resistin-like molecule-alpha (RELMalpha), is a profound vasoconstrictor of the pulmonary circulation and a strong mitogenic factor in pulmonary vascular smooth muscle. To further understand the mechanism of these contractile and mitogenic responses, we examined the effect of HIMF on intracellular Ca(2+) in human pulmonary artery smooth muscle cells (SMC). Ca(2+) imaging in fluo 4-loaded human pulmonary artery SMC revealed that recombinant murine HIMF increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in a sustained and oscillatory manner. This increase occurred independent of extracellular Ca(2+) influx. Pretreatment of human pulmonary artery SMC with U-73122, a specific inhibitor of phosphatidylinositol-phospholipase C (PLC) completely prevented the HIMF-induced Ca(2+) signal. The [Ca(2+)](i) increase was also abolished by pretreatment with 2-aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-trisphosphate (IP(3)) receptor antagonist. Ryanodine pretreatment did not affect initiation of [Ca(2+)](i) activation or internal release but reduced [Ca(2+)](i) at the plateau phase. Pretreatment with the Galpha(i)-specific inhibitor pertussis toxin and the Galpha(s)-specific inhibitor NF-449 did not block the Ca(2+) signal. Knockdown of Galpha(q/11) expression did not prevent Ca(2+) release, but the pattern of Ca(2+) release changed from the sustained oscillatory transients with prolonged plateau to a series of short [Ca(2+)](i) transients that return to baseline. However, pretreatment with the tyrosine kinase inhibitor genistein completely inhibited the internal Ca(2+) release. These results demonstrate that HIMF can stimulate intracellular Ca(2+) release in human pulmonary artery SMC through the PLC signaling pathway in an IP(3)- and tyrosine phosphorylation-dependent manner and that Galpha(q/11) protein-coupled receptor and ryanodine receptor contribute to the increase of [Ca(2+)](i).
 ...
PMID:Hypoxia-induced mitogenic factor/FIZZ1 induces intracellular calcium release through the PLC-IP(3) pathway. 1942 74

We tested the hypothesis that vasomotor control is differentially regulated between feed arteries and downstream arterioles from the cremaster muscle of C57BL/6 mice. In isolated pressurized arteries, confocal Ca(2+) imaging of smooth muscle cells (SMCs) revealed Ca(2+) sparks and Ca(2+) waves. Ryanodine receptor (RyR) antagonists (ryanodine and tetracaine) inhibited both sparks and waves but increased global Ca(2+) and myogenic tone. In arterioles, SMCs exhibited only Ca(2+) waves that were insensitive to ryanodine or tetracaine. Pharmacological interventions indicated that RyRs are functionally coupled to large-conductance, Ca(2+)-activated K(+) channels (BK(Ca)) in SMCs of arteries, whereas BK(Ca) appear functionally coupled to voltage-gated Ca2+ channels in SMCs of arterioles. Inositol 1,4,5-trisphosphate receptor (IP3R) antagonists (xestospongin D or 2-aminoethoxydiphenyl borate) or a phospholipase C inhibitor (U73122) attenuated Ca(2+) waves, global Ca(2+) and myogenic tone in arteries and arterioles but had no effect on arterial sparks. Real-time PCR of isolated SMCs revealed RyR2 as the most abundant isoform transcript; arteries expressed twice the RyR2 but only 65% the RyR3 of arterioles and neither vessel expressed RyR1. Immunofluorescent localisation of RyR protein indicated bright, clustered staining of arterial SMCs in contrast to diffuse staining in arteriolar SMCs. Expression of IP(3)R transcripts and protein immunofluorescence were similar in SMCs of both vessels with IP(3)R1>>IP(3)R2>IP(3)R3. Despite similar expression of IP(3)Rs and dependence of Ca(2+) waves on IP(3)Rs, these data illustrate pronounced regional heterogeneity in function and expression of RyRs between SMCs of the same vascular resistance network. We conclude that vasomotor control is differentially regulated in feed arteries vs. downstream arterioles.
 ...
PMID:Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles. 2233 18

The primary role of fibroblasts is production and degradation of extracellular matrix, and thus it helps in the structural framework of tissues. The close relation between fibroblast malfunction and many diseases such as chronic obstructive pulmonary disease, asthma, and fibrosis is widely accepted. Fibroblasts are known to respond to different growth factors and cytokines including platelet-derived growth factors (PDGF). However, the intracellular signaling mechanisms are not entirely clear. In addition to complex phosphorylation-driven signaling pathways, PDGF is also known to work through Ca(2+) signaling. We hypothesize that in human pulmonary fibroblasts, Ca(2+) waves play an important role in PDGF-mediated changes. To test this hypothesis, we treated human pulmonary fibroblasts, obtained from the lungs of ten donors, with PDGF acutely or overnight plus/minus a variety of blockers under various conditions. Ca(2+) waves were monitored by confocal [Ca(2+)]i fluorimetry, while gene expression of extracellular matrix genes was assessed via RT-PCR method. We found that both acute and overnight PDGF treatment evoked Ca(2+) waves. Removal of external Ca(2+) or depletion of internal Ca(2+) store using Cyclopiazonic acid (CPA) completely occluded PDGF-evoked Ca(2+) waves. Ryanodine, which blocks ryanodine receptor channels, had no effect on PDGF-evoked Ca(2+) wave, whereas the phospholipase C inhibitor U73122 and Xestospongin C, a potent IP3 receptor blocker, reduced the rapid PDGF-response to a relatively slowly-developing rise in [Ca(2+)]i. We also found that PDGF dramatically increased the expression of fibronectin1 and collagen A1 genes, which was reversed by the use of CPA or U73122. Our study indicates that, in human pulmonary fibroblasts, PDGF acts through IP3-induced Ca(2+)-release to trigger Ca(2+) waves, which in turn modulate gene expression of several matrix proteins.
 ...
PMID:Platelet derived growth factor-evoked Ca2+ wave and matrix gene expression through phospholipase C in human pulmonary fibroblast. 2361 77

The role of the system of deposited calcium in the mediation of contractile reactions to carbachol in an isolated amnion of 11-13 day old chicken embryo was studied. It was found that thapsigargin (2 microM, 20 min), an inhibitor of the endoplasmic reticulum Ca2+ -ATPases, decreases the tonic reaction to carbachol by 40 +/- 2%. In the presence of U73122 (5-10 microM, 10 min), a phosphoinositide-specific phospholipase C inhibitor, the rhythmic contractile reaction of the amnion to carbachol is blocked, whereas the tonic reactiondecreases to 47 +/- 9% of the initial one. Ryanodine (10 rM, 5 min) inhibits the spontaneous contractile activity of the amnion and decreases the tonic reaction to carbachol to 36 +/- 3% relative to control. In the presense of ryano- dine, nifedipine (0.05 microM) completely blocks the tonic reaction to carbachol. Thus, calcium mobilized from intracellular stores via inositol trisphosphate and ryanodine receptors is involved in realization of contractile reactions, mediated by M3 receptors, in the chick amnion.
 ...
PMID:[Intracellular transmission of the cholinergic signal in the chick amnion]. 2573 56


<< Previous 1 2