The IGF-1-IGF-1 Receptor System Modulates Myocyte Proliferation but Not Myocyte Cellular Hypertrophy in Vitro

1994 ◽  
Vol 215 (2) ◽  
pp. 273-283 ◽  
Author(s):  
Jan Kajstura ◽  
Wei Cheng ◽  
Krzysztof Reiss ◽  
Piero Anversa
Keyword(s):  
Receptor System ◽  
Cellular Hypertrophy ◽  
Myocyte Proliferation

scholarly journals The Wnt1 ligand/Frizzled 3 receptor system plays a regulatory role in the achievement of the ‘in vitro’ capacitation and subsequent ‘in vitro’ acrosome exocytosis of porcine spermatozoa

Andrology ◽  
2015 ◽  
Vol 3 (2) ◽  
pp. 357-367 ◽  
Author(s):  
A. A. Covarrubias ◽  
M. Yeste ◽  
E. Salazar ◽  
A. Ramírez-Reveco ◽  
J. E. Rodriguez Gil ◽  
...  
Keyword(s):  
Regulatory Role ◽  
Receptor System ◽  
Porcine Spermatozoa

scholarly journals PKA at a Cross-Road of Signaling Pathways Involved in the Regulation of Glioblastoma Migration and Invasion by the Neuropeptides VIP and PACAP

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 123 ◽  
Author(s):  
Souheyla Bensalma ◽  
Soumaya Turpault ◽  
Annie-Claire Balandre ◽  
Madryssa De Boisvilliers ◽  
Afsaneh Gaillard ◽  
...  
Keyword(s):  
Rat Brain ◽  
Ex Vivo ◽  
Brain Parenchyma ◽  
Migration And Invasion ◽  
C6 Cells ◽  
Selective Inhibitors ◽  
Receptor System ◽  
And Migration ◽  
Vip Receptor

Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the “VIP-receptor system”, has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.

Chronically Elevated Endothelin-1 Concentrations Modulate the β-Adrenergic Receptor System In Vitro and In Vivo

2000 ◽  
Vol 36 ◽  
pp. S157-S159
Author(s):  
Bernhard R. Brehm ◽  
Helmut Heinle ◽  
Teut Risler ◽  
Sabine C. Wolf
Keyword(s):  
Adrenergic Receptor ◽  
Receptor System ◽  
Endothelin 1

The mechanism of low molecular weight heparin (LMWH) inhibition of tumor growth

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13093-13093 ◽  
Author(s):  
S. L. Smiley ◽  
D. O. Henry ◽  
M. K. Wong
Keyword(s):  
Endothelial Cells ◽  
Tumor Growth ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Receptor System ◽  
Fgf Receptor ◽  
Tumor Inhibition ◽  
Inhibition Of Tumor Growth

13093 Background: Clinical studies show that LMWHs improve survival in cancer patients. There is compelling and mounting evidence that non-anticoagulation factors are at play, and that these may be contributing in a major way to improved patient outcome. Methods and Results: Dalteparin, enoxaparin, and tinzaparin were tested for their in vivo ability to inhibit tumor lines engineered for aggressive angiogenesis-driven growth. Therapeutic daily doses of drug administered the day following tumor inoculation resulted in significant angiogenesis and tumor inhibition. We previously showed that LMWHs inhibit fibroblast growth factor (FGF) -induced mitogenesis of Tumor Derived Endothelial Cells (TDECs) in a time and concentration dependent manner in vitro. We now show that this endothelial inhibition occurs through LMWHs-mediated reduction of phosphorylation and down stream signaling through ERK. The potency of LMWH was significantly reduced when TDECs were pretreated with heparinase- suggesting that the molecular target for LMWH may be the cell surface, low affinity FGF receptor system. Both our in vivo and in vitro studies demonstrate that angiogenesis and tumor inhibition are greatest for dalteparin > tinzaparin > enoxaparin. Clues to the heparin-TDECs interaction comes from tracking the real-time movement of FGF using a highly fluorescent nanocrystal bead decorated on its surface with FGF. High resolution video-microscopy shows FGF binding onto TDEC surfaces, but once heparin enters the environment, FGF detaches from the TDECs and migrates to the heparin. This ultimately results in significant TDEC growth inhibition as compared to controls. Conclusion: LMWH treatment at pharmacologic doses significantly blunts tumor growth and angiogenesis. This inhibition resides in part via heparin’s ability to sequester FGF from the low affinity receptor system on tumor endothelial cells. No significant financial relationships to disclose.

scholarly journals IGF-I Regulates Pheochromocytoma Cell Proliferation and Survival In Vitro and In Vivo

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3724-3734 ◽  
Author(s):  
María Celia Fernández ◽  
Marcela Venara ◽  
Susana Nowicki ◽  
Héctor E. Chemes ◽  
Marta Barontini ◽  
...  
Keyword(s):  
Critical Role ◽  
Tumor Development ◽  
Receptor Expression ◽  
Vascular Density ◽  
Receptor System ◽  
Igf I ◽  
Tumor Phenotype ◽  
The Impact

IGFs are involved in malignant transformation and growth of several tissues, including the adrenal medulla. The present study was designed to evaluate the impact of IGF-I on pheochromocytoma development. We used a murine pheochromocytoma (MPC) cell line (MPC4/30) and an animal model with a reduction of 75% in circulating IGF-I levels [liver-IGF-I-deficient (LID) mice] to perform studies in vitro and in vivo. We found that, in culture, IGF-I stimulation increases proliferation, migration, and anchorage-independent growth, whereas it inhibits apoptosis of MPC cells. When injected to control and to LID mice, MPC cells grow and form tumors with features of pheochromocytoma. Six weeks after cell inoculation, all control mice developed sc tumors. In contrast, in 73% of LID mice, tumor development was delayed to 7–12 wk, and the remaining 27% did not develop tumors up to 12 wk after inoculation. LID mice harboring MPC cells and treated with recombinant human IGF-I (LID+) developed tumors as controls. Tumors developed in control, LID, and LID+ mice had similar histology and were similarly positive for IGF-I receptor expression. The apoptotic index was higher in tumors from LID mice compared with those from control mice, whereas vascular density was decreased. In summary, our work demonstrates that IGF-I has a critical role in maintaining tumor phenotype and survival of already transformed pheochromocytoma cells and is required for the initial establishment of these tumors, providing encouragement to carry on research studies to address the IGF-I/IGF-I receptor system as a target of therapeutic strategies for pheochromocytoma treatment in the future.

Galactopoietic and mammogenic effects of long-term treatment with bovine growth hormone and thrice daily milking in goats

1990 ◽  
Vol 127 (1) ◽  
pp. 129-138 ◽  
Author(s):  
C. H. Knight ◽  
P. A. Fowler ◽  
C. J. Wilde
Keyword(s):  
Enzyme Activities ◽  
Combined Treatment ◽  
Cell Number ◽  
Term Treatment ◽  
Whole Body ◽  
Whole Body Imaging ◽  
In Vitro Synthesis ◽  
Cellular Hypertrophy ◽  
Long Term Treatment

ABSTRACT Starting in mid-lactation, goats were treated daily for 22 weeks with 0·15 mg recombinant bovine GH (bGH)/kg, or an equivalent volume of vehicle. One gland of each goat was milked thrice daily throughout treatment, the other twice daily. Mammary differentiation was studied in biopsy samples obtained before treatment and after 3 and 22 weeks of treatment, by determination of in-vitro synthesis rates of milk constituents and measurement of enzyme activities. Mammary growth was measured using a whole-body imaging technique (magnetic resonance imaging; MRI). bGH caused an immediate and sustained increase in milk yield of approximately 23% overall, whilst the glands milked thrice daily produced approximately 14% more than the control glands milked twice daily. The effects of the combined treatment were additive, but not synergistic. A synergistic effect of the combined treatment resulted in a significant improvement in lactation persistency. A stimulatory effect of milking frequency on mammary enzyme activities was evident only in bGH-treated goats at 3 weeks, but in both groups at 22 weeks. Synthesis rates of casein and lactose were increased at 3 weeks only by the combined treatment. Thus bGH accelerated or augmented the differentiative response to thrice daily milking. Mammary parenchyma volume, estimated by MRI, increased significantly during the first 12 weeks of bGH treatment and remained higher throughout the rest of the treatment period. Cell number was estimated from parenchyma volume and DNA concentration; this decreased significantly in the controls between weeks 1 and 22, but remained constant in the bGH group. In nine of the ten goats, parenchyma volume and cell number increased in the gland milked thrice daily relative to the control gland milked twice daily during the course of the experiment. Thus bGH stimulated growth of the mammary gland over and above that induced by the frequent milking. The absence of any detectable increase in thymidine incorporation suggests that this growth consisted of cellular hypertrophy rather than hyperplasia. Journal of Endocrinology (1990) 127, 129–138

scholarly journals Postnatal - Physiological Research of the Bronchial Receptor System Development on the Isolated Preparation of The Human Trachea In Vitro

2006 ◽  
Vol 6 (3) ◽  
pp. 73-77
Author(s):  
Aziz Šukalo ◽  
Hilmi Islami ◽  
Ragib Shabani ◽  
Hilmi Dauti ◽  
Skender Kutllovci ◽  
...  
Keyword(s):  
System Development ◽  
Newborn Infants ◽  
Smooth Muscles ◽  
Adrenergic System ◽  
Receptor System ◽  
Intrauterine Life ◽  
Isolated Trachea ◽  
Human Trachea ◽  
Physiological Research

Research was done on pharmacological-physiological development of the bronchial receptor system on the smooth muscles of trachea in the newborn children, alive-born and stillborn children. Monitored was the response on: acetylcholine, dopamine, histamine and serotonin in different molar concentrations 10(-4), 10(-3), 10(-2), 10 mol/dm(-3), micromol/dm(-3)). Research was done on tonus of tracheal smooth muscles of 23 tracheal preparations taken by autopsy after death from different factors. Based on pharmacological-physiological research on the preparations of human isolated trachea it was find out that: acetylcholine stimulation effect is significant (p>0,01) in 38-41 weeks of pregnancy comparing with that in 30-37 weeks of pregnancy (p>0,01), while dopamine stimulation effect is significant (p>0,05) in 30-37 pregnancy weeks comparing with the effect of acetylcholine and dopamine on the still-born infants of the same pregnancy period (p<0,01). Histaminic receptors were developed during intrauterine life after 38 weeks of pregnancy (p>0,025). Serotonin has caused contraction of the bronchial smooth muscles after 30 pregnancy weeks, but response was not significant (p<0,01). This suggests that cholinergic and adrenergic system of the airways in alive newborn infants develops in parallel intrauterine, contrary to other systems which develop in certain extrauterine life phases.

Abstract 68: p38 MAP Kinase Regulates Chamber Specific Postnatal Remodelling of Cardiac Ventricles

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Tomohiro Yokota ◽  
Jin Li ◽  
Qing Zhang ◽  
Yichen Ding ◽  
Kevin Sung ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Activity ◽  
P38 Map Kinase ◽  
Mouse Heart ◽  
Neonatal Lethality ◽  
Cardiac Ventricles ◽  
Inner Diameter ◽  
Apoptotic Activity ◽  
Myocyte Proliferation

Background: Left ventricle (LV) and right ventricle (RV) in mouse heart undergo dramatically different chamber-specific remodeling after birth, leading to rapid increase in LV vs. RV chamber size. However, the underlying regulatory mechanism mediating chamber specific remodeling process remains enigmatic. Results and Methods: In neonatal mouse heart, p38 MAP kinase activity is dynamically activated in a chamber specific manner. p38 activity is specifically elevated in RV comparing to LV at E18.5, postnatal day 3 (P3) and P7 stages whereas p38 activity is lower in both ventricles at P0 and P1. In mouse heart with cardiomyocyte specific-knockout of p38α and β (p38ab-cdKO), total p38 activity was diminished in both chambers. The p38ab-cdKO mice had significant neonatal lethality associated with RV specific chamber enlargement and significant increase in both RV wall thickness (RVW) and inner diameter of RV (RVID) as early as P3. Interestingly, p38 inactivation suppressed myocyte apoptotic activity specifically in RV while increased RV myocyte proliferation and hypertrophy during neonatal period. Unexpectedly, RNA-seq results implicated Xbp1 mediated transcriptional regulation significantly contributing to p38 dependent transcriptome reprogramming in RV. Indeed, IRE1α expression in neonatal cardiomyocyte is sufficient to induce proliferation in vitro. Furthermore, knockdown of Xbp1 blunted p38 inhibition-induced myocyte proliferation, suggesting that IRE1a/Xbp1 mediate p38 signaling in neonatal myocyte proliferation. Conclusion: Chamber-specific remodeling in neonatal heart involves temporally regulated and RV specific p38 MAP kinase activity. RV specific myocyte proliferation and hypertrophy concurrent with RV specific programmed myocyte death is orchestrated by two innate stress-response pathways, p38 and Xbp1.

Sign in / Sign up

Export Citation Format

Share Document