scholarly journals 5-HT1A and histamine H1 receptors in HeLa cells stimulate phosphoinositide hydrolysis and phosphate uptake via distinct G protein pools.

1991 ◽  
Vol 266 (1) ◽  
pp. 372-379 ◽  
Author(s):  
J R Raymond ◽  
F J Albers ◽  
J P Middleton ◽  
R J Lefkowitz ◽  
M G Caron ◽  
...  
Keyword(s):  
G Protein ◽  
Hela Cells ◽  
Phosphate Uptake ◽  
Phosphoinositide Hydrolysis ◽  
Histamine H1 Receptors

scholarly journals Epidermal growth factor-induced phosphoinositide hydrolysis in permeabilized 3T3 cells: lack of guanosine triphosphate dependence and inhibition by tyrosine-containing peptides.

1990 ◽  
Vol 1 (9) ◽  
pp. 615-620 ◽  
Author(s):  
G F Verheijden ◽  
I Verlaan ◽  
J Schlessinger ◽  
W H Moolenaar
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
G Protein ◽  
Egf Receptor ◽  
Phosphoinositide Hydrolysis ◽  
3T3 Cells ◽  
Guanosine Triphosphate ◽  
Intact Cells ◽  
Epidermal Growth ◽  
Gamma S

The possible involvement of a stimulatory guanosine triphosphate (GTP)-binding (G) protein in epidermal growth factor (EGF)-induced phosphoinositide hydrolysis has been investigated in permeabilized NIH-3T3 cells expressing the human EGF receptor. The mitogenic phospholipid lysophosphatidate (LPA), a potent inducer of phosphoinositide hydrolysis, was used as a control stimulus. In intact cells, pertussis toxin partially inhibits the LPA-induced formation of inositol phosphates, but has no effect on the response to EGF. In cells permeabilized with streptolysin-O, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) dramatically increases the initial rate of inositol phosphate formation induced by LPA. In contrast, activation of phospholipase C (PLC) by EGF occurs in a GTP-independent manner. Guanine 5'-O-(2-thiodiphosphate) (GDP beta S) which keeps G proteins in their inactive state, blocks the stimulation by LPA and GTP gamma S, but fails to affect the EGF-induced response. Tyrosine-containing substrate peptides, when added to permeabilized cells, inhibit EGF-induced phosphoinositide hydrolysis without interfering with the response to LPA and GTP gamma S. These data suggest that the EGF receptor does not utilize an intermediary G protein to activate PLC and that receptor-mediated activation of effector systems can be inhibited by exogenous substrate peptides.

GNG11 (G-protein subunit γ 11) suppresses cell growth with induction of reactive oxygen species and abnormal nuclear morphology in human SUSM-1 cells

2017 ◽  
Vol 95 (4) ◽  
pp. 517-523 ◽  
Author(s):  
Yuki Takauji ◽  
Ikuru Kudo ◽  
Atsuki En ◽  
Ryo Matsuo ◽  
Mohammad Nazir Hossain ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
G Protein ◽  
Cell Lines ◽  
Hela Cells ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Nuclear Morphology ◽  
Oxygen Species ◽  
Protein Subunit ◽  
Regulatory Relationship

Enforced expression of GNG11, G-protein subunit γ 11, induces cellular senescence in normal human diploid fibroblasts. We here examined the effect of the expression of GNG11 on the growth of immortalized human cell lines, and found that it suppressed the growth of SUSM-1 cells, but not of HeLa cells. We then compared these two cell lines to understand the molecular basis for the action of GNG11. We found that expression of GNG11 induced the generation of reactive oxygen species (ROS) and abnormal nuclear morphology in SUSM-1 cells but not in HeLa cells. Increased ROS generation by GNG11 would likely be caused by the down-regulation of the antioxidant enzymes in SUSM-1 cells. We also found that SUSM-1 cells, even under normal culture conditions, showed higher levels of ROS and higher incidence of abnormal nuclear morphology than HeLa cells, and that abnormal nuclear morphology was relevant to the increased ROS generation in SUSM-1 cells. Thus, SUSM-1 and HeLa cells showed differences in the regulation of ROS and nuclear morphology, which might account for their different responses to the expression of GNG11. Thus, SUSM-1 cells may provide a unique system to study the regulatory relationship between ROS generation, nuclear morphology, and G-protein signaling.

Histamine H1-receptors mediate phosphoinositide hydrolysis in astrocyte-enriched primary cultures

1988 ◽  
Vol 450 (1-2) ◽  
pp. 144-152 ◽  
Author(s):  
Lourdes Arbonés ◽  
Fernando Picatoste ◽  
Agustina García
Keyword(s):  
Primary Cultures ◽  
Phosphoinositide Hydrolysis ◽  
Histamine H1 Receptors

scholarly journals Pleckstrin Inhibits Phosphoinositide Hydrolysis Initiated by G-protein-coupled and Growth Factor Receptors. A ROLE FOR PLECKSTRIN'S PH DOMAINS

1995 ◽  
Vol 270 (24) ◽  
pp. 14485-14492 ◽  
Author(s):  
Charles S. Abrams ◽  
Hung Wu ◽  
Wei Zhao ◽  
Elizabeth Belmonte ◽  
David White ◽  
...  
Keyword(s):  
Growth Factor ◽  
G Protein ◽  
Growth Factor Receptors ◽  
Phosphoinositide Hydrolysis ◽  
Ph Domains ◽  
G Protein Coupled

scholarly journals Intracellular elevations of free calcium induced by activation of histamine H1 receptors in interphase and mitotic HeLa cells: hormone signal transduction is altered during mitosis.

1988 ◽  
Vol 107 (6) ◽  
pp. 2533-2539 ◽  
Author(s):  
M Volpi ◽  
R D Berlin
Keyword(s):  
Signal Transduction ◽  
Intracellular Calcium ◽  
Hela Cells ◽  
Calcium Influx ◽  
Tumor Promoter ◽  
Free Calcium ◽  
Interphase Cells ◽  
Underlying Mechanisms ◽  
Histamine H1 Receptors ◽  
Transient Elevation

A broad range of membrane functions, including endocytosis and exocytosis, are strongly inhibited during mitosis. The underlying mechanisms are unclear, however, but will probably be important in relation to the mitotic cycle and the regulation of surface phenomena generally. A major unanswered question is whether membrane signal transduction is altered during mitosis; suppression of an intracellular calcium [( Ca2+]i) transient could inhibit exocytosis; [Ca2+]i elevation could disassemble the mitotic spindle. Activation of the histamine H1 receptor interphase in HeLa cells is shown here by Indo-1 fluorescence to produce a transient elevation of [Ca2+]i. The [Ca2+]i transient consists of an initial sharp rise that is at least partially dependent on intracellular calcium followed by an elevated plateau that is absolutely dependent on extracellular calcium. The [Ca2+]i transient is completely suppressed by preincubation with the tumor promoter, phorbol myristate acetate, but is unaffected by preincubation with pertussis toxin (islet-activating protein). In mitotic (metaphase-arrested) HeLa cells, the [Ca2+]i transient is largely limited to the initial peak. Measurement of 45Ca2+ uptake shows that it is stimulated by histamine in interphase cells, but not in mitotics. We conclude that the histamine-stimulated generation of the second messenger, [Ca2+]i, in mitotic cells is limited by failure to activate a sustained calcium influx. The initial phase of calcium mobilization from intracellular stores is comparable to that in interphase cells. Hormone signal transduction thus appears to be altered during mitosis.

Annexin II inhibition of G protein-regulated inositol trisphosphate formation in rat aortic smooth muscle

1996 ◽  
Vol 270 (4) ◽  
pp. F682-F690 ◽  
Author(s):  
J. R. Schelling ◽  
D. J. Gentry ◽  
G. R. Dubyak
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
G Protein ◽  
Inositol Trisphosphate ◽  
Phosphoinositide Hydrolysis ◽  
Annexin Ii ◽  
Mechanism Of Inhibition ◽  
Intracellular Signals ◽  
Gamma S ◽  
G Protein Coupled

Vasoconstrictor hormones contribute to the pathogenesis of hypertension through intracellular signals that stimulate vascular smooth muscle (VSMC) contraction and/or growth. We previously showed that the glucocorticoid dexamethasone (DEX) inhibited angiotensin II-stimulated inositol trisphosphate (IP3) formation in VSMC, but the mechanism of inhibition is not known. Because glucocorticoids stimulate the expression of annexins and annexin II potently binds phosphoinositides, the role of DEX and annexin II in VSMC G protein-coupled phosphoinositide hydrolysis was investigated. DEX incubation blunted increases in guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)-stimulated IP3 generation and angiotensin II-induced intracellular Ca2+ mobilization but stimulated elevations in VSMC annexin II content. VSMC incubation with exogenous purified annexin II resulted in concentration-dependent decreases in GTP gamma S-stimulated IP3 formation. In DEX-treated cells, exogenous annexin II did not further diminish GTP gamma S-stimulated IP3 formation, suggesting that endogenous annexin II may be a mediator of DEX-induced inhibition of G protein-coupled IP3 generation. These data represent the first direct evidence of G protein-dependent phosphoinositide hydrolysis regulation by glucocorticoids or annexins. We speculate that annexin II may play a role in the pathogenesis of hypertension through stimulation of VSMC growth.

Receptor-G-protein signalling in Alzheimer's disease

2001 ◽  
Vol 67 ◽  
pp. 163-175 ◽  
Author(s):  
Richard F. Cowburn ◽  
Cora O'Neill ◽  
Willy L. Bonkale ◽  
Thomas G. Ohm ◽  
Johan Fastbom
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
G Protein ◽  
Radioligand Binding ◽  
Phosphoinositide Hydrolysis ◽  
Binding Studies ◽  
Neurofibrillary Changes ◽  
Hydrolysis Pathway ◽  
Stimulation Of

Based on radioligand binding studies, it has long been assumed that the neurochemical pathology of Alzheimer's disease (AD) does not involve widespread changes in post-synaptic neurotransmitter function. However, more recent studies suggest that receptor function in AD may be compromised due to disrupted post-receptor signal transduction, in particular that mediated by the G-protein regulated phosphoinositide hydrolysis and adenylate cyclase (AC) pathways. The phosphoinositide hydrolysis pathway has been shown to be altered at a number of levels in AD post-mortem brains, including impaired agonist and G-protein regulation of phospholipase C, decreased protein kinase C (PKC) levels and activity, and a reduced number of receptor sites for the second messenger, Ins(1,4,5)P3. Of these, loss of Ins(1,4,5)P3 receptors and PKC in the entorhinal cortex and hippocampus correlates with AD-related neurofibrillary changes, as staged according to Braak's protocol. Disregulation of the phosphoinositide hydrolysis pathway may therefore have consequences for the progression of AD pathology. In contrast to the extensive pattern of disruption seen with the phosphoinositide hydrolysis pathway, changes to AC signalling in AD appear more circumscribed. Disruptions include a lesion at the level of Gs-protein stimulation of AC and, at least in the hippocampus, reduced enzyme activities in response to forskolin stimulation. Of these, the latter change has been shown to precede neurofibrillary changes. Apart from a loss of calcium/calmodulin sensitive AC isoforms, other components of this signalling pathway, including G-protein levels, Gi-protein mediated inhibition and protein kinase A levels and activity, remain relatively preserved in the disorder.

P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G protein-dependent mechanism

1996 ◽  
Vol 271 (5) ◽  
pp. R1101-R1101
Author(s):  
E. D. Lederer ◽  
K. R. McLeish
Keyword(s):  
G Protein ◽  
American Heart Association ◽  
American Heart ◽  
Phosphate Uptake ◽  
Heart Association ◽  
Dependent Mechanism

Pages F309–F316: E. D. Lederer and K. R. McLeish. ”P2 purinoceptor stimulation attenuates PTH inhibition of phosphate uptake by a G protein-dependent mechanism.“ The American Heart Association of Kentucky should have been acknowledged for their support of E. D. Lederer.

Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins

1993 ◽  
Vol 136 (3) ◽  
pp. 497-NP ◽  
Author(s):  
S. Phaneuf ◽  
G. N. Europe-Finner ◽  
M. Varney ◽  
I. Z. MacKenzie ◽  
S. P. Watson ◽  
...  
Keyword(s):  
G Protein ◽  
Pertussis Toxin ◽  
Inositol Phosphates ◽  
Phosphoinositide Hydrolysis ◽  
Maximal Response ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Myometrial Cells ◽  
Uterine Contractions

ABSTRACT Phosphoinositide hydrolysis is important in mediating the actions of oxytocin and prostaglandin (PG) F2α on uterine contractions during labour. We have measured the effect of oxytocin, PGF2α and other agents on the formation of inositol phosphates (IPs) in cultured human myometrial cells labelled with [3H]inositol and on changes in intracellular free Ca2+ concentration ([Ca2 + ]i) in cells loaded with Fura-2. Oxytocin induced the formation of [3H]IPs in a concentration-dependent manner with an EC50 (concentration of agonist producing 50% of the maximal response) of 1·4 ±0·5 nmol/l (mean ± s.e.m.). The maximal response was obtained with 1 μmol oxytocin/l and represented a stimulation of 670% over basal. PGF2α also stimulated the formation of [3H]IPs and the response at 1 μmol/l was a 204% stimulation over basal. The effects of PGF2α were independent of extracellular Ca2 + but the effect of oxytocin was reduced with low extracellular Ca2 +. Cyclic AMP formation, induced by forskolin or PGE2, had no effect on the stimulated levels of [3H]IPs. Pertussis toxin (PT) reduced the oxytocin-stimulated formation of [3H]IPs in a concentration-dependent manner. The maximal effect of PT resulted in an 80% reduction in the formation of [3H]IPs. However, PGF2α stimulation was not affected by PT treatment. To analyse the action of PT further, we studied its effect on oxytocin-induced changes in [Ca2 + ]i. The basal [Ca2 +]i was 112 ±4 nmol/l (n=225 cells) and was not affected by PT treatment (109 ± 3 nmol/l; n= 200 cells). In the absence of PT, 1 μmol oxytocin/l increased [Ca2 + ]i to a peak of 522 ±26 nmol/l, and in PT-treated cells, the [Ca2 + ]i peak was reduced to 348 ± 16 nmol/l. Similar inhibitory effects of PT were obtained at oxytocin concentrations ranging from 1 to 100 nmol/l. Our data suggest that in human myometrial cells, the oxytocin-induced production of [3H]IPs and increase in [Ca2 + ]i are mediated by a PT-sensitive G-protein. However, a significant fraction of the oxytocin response appears to be mediated by a PT-insensitive G-protein, possibly a member of the Gq family. Journal of Endocrinology (1993) 136, 497–509

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