scholarly journals Insulin-like growth factor-I (IGF-I) antisense oligodeoxynucleotide mediated inhibition of DNA synthesis by WI-38 cells: evidence for autocrine actions of IGF-I.

1993 ◽  
Vol 7 (2) ◽  
pp. 171-180
Author(s):  
B M Moats-Staats ◽  
G Z Retsch-Bogart ◽  
W A Price ◽  
H W Jarvis ◽  
A J D'Ercole ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Antisense Oligodeoxynucleotide ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Inhibition Of Dna Synthesis

Insulin-like Growth Factor I Regulates Apoptosis in Condylar Cartilage

2008 ◽  
Vol 87 (2) ◽  
pp. 159-163 ◽  
Author(s):  
T. Yokota ◽  
H. Shimokawa ◽  
S. Shibata ◽  
K. Itoh ◽  
Y. Baba ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Layer ◽  
Mesenchymal Cell ◽  
Antisense Oligodeoxynucleotide ◽  
Insulin Like Growth Factor ◽  
Condylar Cartilage ◽  
Factor I ◽  
Igf I ◽  
Undifferentiated Mesenchymal Cell ◽  
Growth Factor I

Endogenous insulin-like growth factor-I (IGF-I) is known to affect the growth and development of condylar cartilage. However, the critical effect of IGF-I on cell survival is still unknown. We hypothesized that endogenous IGF-I could regulate the survival of cells of the mandibular condylar cartilage. Mandibular condyles dissected from 12-day-old rats were cultured for 1, 3, and 5 days in medium containing antisense oligodeoxynucleotide (AS-ODN) for IGF-I. Real-time RT-PCR analysis showed that the levels of IGF-I and IGF binding protein (IGFBP)3 mRNAs in the AS-ODN group were significantly decreased. After 3 days’ culture, the number of necrotic cells was observed in the undifferentiated mesenchymal cell layer. These cells were TUNEL-positive and confirmed to be apoptotic by electron microscopic observation. Immunoblotting revealed that expression of cleaved caspase3 was increased with AS-ODN. These results may suggest that the cells in the undifferentiated mesenchymal cell layer of the mandibular condyle require IGF-I for survival.

scholarly journals Activation of the phosphatidylinositol-3' kinase pathway and DNA synthesis by a mutant insulin-like growth factor I receptor lacking the NPXY motif

2004 ◽  
Vol 181 (1) ◽  
pp. 139-146 ◽  
Author(s):  
K Kataoka ◽  
D Yu ◽  
M Miura
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Cell Lines ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Factor I ◽  
Igf I ◽  
Npxy Motif ◽  
Growth Factor I ◽  
Phosphatidylinositol 3

We have investigated the role of the NPXY motif in the insulin-like growth factor I receptor (IGF-IR) by focusing on the activation of the phosphatidylinositol-3' kinase (PI3-K) pathway and DNA synthesis following IGF-I stimulation. For this purpose, we established stable R-cell lines, which are deficient in endogenous IGF-IR, and express human IGF-IR lacking the whole NPEY(950) sequence (DeltaNPEY). The DeltaNPEY cells showed an apparent autophosphorylation of IGF-IR, albeit with reduced sensitivity to stimulation compared with cells expressing similar levels of wild-type IGF-IR. Activation of insulin receptor substrate (IRS)-1 and IRS-2 was severely impaired in DeltaNPEY cells even at high concentrations of IGF-I. However, recruitment of p85, a regulatory subunit of PI3-K, to activated IRS-2 was similar between the cell lines, but recruitment of p85 to IRS-1 was reduced in DeltaNPEY cells. Essentially similar levels of p85- or phosphotyrosine-associated PI3-K and Akt activities were observed between the cell lines, although the sensitivity to stimulation was reduced in DeltaNPEY cells. Activation of extracellular signal-regulated kinase and DNA synthesis were virtually unaffected by the mutation, in terms of both sensitivity to stimulation and responsiveness. DNA synthesis was completely inhibited by the PI3-K inhibitor, LY294002. These results indicate that the IGF-IR is able to activate the PI3-K pathway and induce DNA synthesis in a normal fashion without the NPXY motif when the receptor is fully activated.

scholarly journals Zinc Deprivation of Murine 3T3 Cells by Use of Diethylenetrinitrilopentaacetate Impairs DNA Synthesis upon Stimulation with Insulin-Like Growth Factor-I (IGF-I)

1998 ◽  
Vol 128 (10) ◽  
pp. 1600-1605 ◽  
Author(s):  
Ruth S. MacDonald ◽  
Lavonna C. Wollard-Biddle ◽  
Jimmy D. Browning ◽  
William H. Thornton ◽  
Boyd L. O'Dell
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Insulin Like Growth Factor ◽  
3T3 Cells ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line RINm5F is associated with phosphorylation of the insulin-like growth factor-I receptor and the insulin receptor substrate-2

1998 ◽  
Vol 156 (3) ◽  
pp. 573-581 ◽  
Author(s):  
Q Zhang ◽  
PO Berggren ◽  
A Hansson ◽  
M Tally
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Insulin Receptor ◽  
Cell Line ◽  
Insulin Receptor Substrate ◽  
Insulin Like Growth Factor ◽  
Rinm5f Cells ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

A proliferative effect of insulin-like growth factor-I (IGF-I) was previously shown in pancreatic islets. However, the mechanism under which IGF-I actions are exerted in insulin-secreting cells is not clear. The rat insulinoma cell line, RINm5F, was shown to have both IGF-I receptors and IGF-Il/mannose-6-phosphate receptors. IGF-I binding to cell surface receptors stimulated phosphorylation of 97 kDa and 93 kDa subunits of the IGF-I receptor and incorporation of [3H]thymidine into RINm5F cells. Both the IGF-I-induced protein phosphorylation and [3H]thymidine incorporation were abolished in the presence of the tyrosine kinase inhibitor, genistein. Under basal conditions, IGF-I did not induce insulin release or changes in cytosolic free Ca2+ concentration. Immunoprecipitation of proteins from RINm5F cells, using phosphotyrosine antibodies, followed by western blotting using antibody against IRS-1 revealed no distinct band of phosphorylated insulin receptor substrate (IRS)-1. Instead, tyrosine-phosphorylated IRS-2 was detected and stimulated by IGF-I when western blotting was performed using antibody against IRS-2. These results indicate that IRS-1 is not likely to be involved in IGF-I signalling in RINm5F cells. Hence, IGF-I stimulated DNA synthesis in RINm5F cells was associated with phosphorylation of IGF-I receptors and IRS-2.

Co-ordinate actions of FSH and insulin-like growth factor-I on LH receptor expression in rat granulosa cells

1994 ◽  
Vol 141 (2) ◽  
pp. 301-308 ◽  
Author(s):  
M Kanzaki ◽  
M-A Hattori ◽  
R Horiuchi ◽  
I Kojima
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Granulosa Cells ◽  
Receptor Expression ◽  
Continuous Exposure ◽  
Insulin Like Growth Factor ◽  
Lh Receptor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 μg FSH/l (high FSH) but not 20 μg FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture. DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I. A similar increase in DNA synthesis was observed after 48 h when granulosa cells were treated with low FSH alone, which did not induce LH receptor expression. These results indicate that 1) growth and differentiation of granulosa cells are regulated inversely; 2) FSH and IGF-I act together to induce LH receptor expression; and 3) action of IGF-I is dependent on the presence of FSH. Journal of Endocrinology (1994) 141, 301–308

scholarly journals Signalling pathways of insulin-like growth factor-I that are augmented by cAMP in FRTL-5 cells

2000 ◽  
Vol 348 (2) ◽  
pp. 409-416 ◽  
Author(s):  
Miyako ARIGA ◽  
Taku NEDACHI ◽  
Masakazu AKAHORI ◽  
Hideki SAKAMOTO ◽  
Yoshiaki ITO ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Map Kinase ◽  
Tyrosine Phosphorylation ◽  
Signalling Pathways ◽  
Insulin Like Growth Factor ◽  
Dibutyryl Camp ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

We have reported that pretreatment of rat FRTL-5 thyroid cells with thyrotropin (TSH) markedly potentiates the mitogenic response to insulin-like growth factor-I (IGF-I). The present study was undertaken to determine whether the augmentation by cAMP of IGF-I-dependent tyrosine phosphorylation of known IGF-I receptor substrates plays an important role in the cAMP-dependent potentiation of DNA synthesis induced by IGF-I. Pretreatment with TSH or dibutyryl cAMP did not affect the IGF-I-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). In contrast, cAMP pretreatment potentiated the tyrosine phosphorylation of IRS-2 induced by IGF-I, but did not affect the amount of IRS-2. We found that the IGF-I-dependent tyrosine phosphorylation of 66 kDa Shc (Src homology collagen) was markedly increased by cAMP pretreatment, and that this change was mainly due to an increase in the levels of 66 kDa Shc protein. Under these conditions, cAMP pretreatment significantly increased binding of Grb2 (growth-factor-receptor-bound protein 2) to Shc in response to IGF-I, and activation of MAP kinase (mitogen-activated protein kinase) induced by IGF-I was also enhanced by cAMP. The presence of PD98059, an inhibitor of MEK (MAP-kinase/Erk kinase), during treatment with IGF-I partially inhibited the cAMP-dependent augmentation of DNA synthesis in response to IGF-I. On the other hand, cAMP pretreatment increased binding of the phosphoinositide 3-kinase (PI 3-kinase) p85 subunit to IRS-2, which was reflected in PI 3-kinase activity. LY294002, a PI 3-kinase inhibitor, strongly depressed IGF-I-dependent DNA synthesis after pretreatment with and without TSH or dibutyryl cAMP. Our results suggest that the interaction between cAMP-dependent and IGF-I-dependent pathways leads to an augmentation of cell proliferation, which is mediated, at least in part, through the MAP kinase and PI 3-kinase signalling pathways. These effects are mediated by changes in tyrosine phosphorylation of IGF-I receptor substrates, including IRS-2 and Shc.

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