Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures

Lenoir, David Paul; Honegger, Paul

doi:10.1016/0165-3806(83)90177-3

Cited by 234 publications

(88 citation statements)

References 31 publications

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“…In our study IGF I was 5 S times more potent than IGF H. These results are in agreement with previous work by Lenoir and Honegger (1983), who observed that IGF I was significantly more potent than IGF II and insulin for stimulating thymidine incorporation 2-fold in fetal rat brain cells cultured in a chemically defined medium. Recently, McMorris et al (1986) In these studies IGF I was also much more potent that insulin.…”

supporting

confidence: 83%

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

et al. 1987

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Gene expression, receptor binding and growth-promoting activity of insulin-like growth factor I (IGF I) was studied in cultured astrocytes from developing rat brain. Northern blot analysis of poly(A)+ RNAs from astrocytes revealed an IGF I mRNA of 1.9 kb. Competitive binding and receptor labelling techniques revealed two types of IGF receptor in astroglial cells. Type I IGF receptors consist of a-subunits (Mr 130 000) which bind IGF I with significantly higher affinity than IGF 11, and fl-subunits (Mr 94 000) which show IGF Isensitive tyrosine kinase activity. Type II IGF receptors are monomers (Mr 250 000) which bind IGF H with three times higher affinity than IGF I. Both types of IGF receptor recognize insulin weakly. DNA synthesis measured by cellular thymidine incorporation was stimulated 2-fold by IGF I and IGF H. IGF I was more potent than IGF H, and both were significantly more potent than insulin. Our findings suggest that IGF I is synthesized in fetal rat astrocytes and acts as a growth promoter for the same cells by activation of the type I IGF receptor tyrosine kinase. We propose that IGF I acts through autocrine or paracrine mechanisms to stimulate astroglial cell growth during normal brain development.

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supporting

confidence: 83%

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

et al. 1987

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“…Moreover, concentrations of IGFs required for the half maximal effect on growth of CFU-E are very similar to that on growth of fetal fibroblasts, chondrocytes, bone cells (cf. reference 25), and brain cells (28).…”

Section: Resultsmentioning

confidence: 99%

Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

Kurtz¹,

Hartl²,

Jelkmann³

et al. 1985

J. Clin. Invest.

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In the present study, the erythropoietic activity of fetal serum was characterized. Using fetal bovine serum (FBS) as a source of the erythropoietic activity and serum-free cultures of fetal mouse livers (FMLC assay) as a detection system, we found that FBS stimulated colony formation from late erythroid progenitor cells (CFU-E) in a dose-dependent fashion. The slope of the dose-response curve, however, was significantly different from that for erythropoietin (Ep), the best-characterized erythropoietic activity so far. The erythropoietic activity of FBS was found in the 120-160-and 40-70-kD range at neutral pH. In the presence of 1 M acetic acid, however, the erythropoietic activity had an apparent molecular mass between 3 and 13 kD. From ion exchange experiments with DEAE-cellulose, the isoionic point of the activity was estimated to about pH 5. Furthermore, the erythropoietic activity of FBS was found to be co-eluted on Sephadex G-150 with the binding proteins of insulinlike growth factors (IGF). The IGF I concentration determined by radioimmunoassay was 70 ng IGF I/ml. The Ep activity of FBS was <5 mU/ml when determined with the posthypoxic polycythemic mouse assay for Ep. These results suggest that the erythropoietic activity of FBS is related to IGF and not to Ep. The erythropoietic activity of FBS was abolished by an antiserum against IGF I. Furthermore, IGF I was a factor of -40 more potent than IGF II in stimulating erythroid colony formation. All of these findings suggest that the erythropoietic activity of FBS is IGF I.

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“…Because they can be isolated and cultured as a relatively homogeneous population (McCarthy and de Vellis, 1980), definitive characterization on a single-cell population is possible. Receptors for Sm/IGFs have been previously identified in neural tissues from various brain regions in rats (Lenoir and Honegger, 1983), both fetal and adult (Sara et al, 1982(Sara et al, , 1984. Because these studies were performed on membrane fractions prepared from whole tissues or explant cultures, however, the specific neural cells possessing Sm/IGF receptors could not be identified.…”

Section: Discussionmentioning

confidence: 99%

“…Sara et al (198 1) postulated that a form of somatomedin (termed human embryonic somatomedin) stimulates growth of human fetal brain cells in vitro and showed that both fetal and adult human brain tissue contains receptors to Sm/IGFs (Sara et al, 1982(Sara et al, , 1983. Synthesis of Sm/IGFs by cultured brain cells has been demonstrated (Binoux et al, 198 1;Birch et al, 1984) and cultured neural tissues can respond to Sm/IGFs (Westermark and Wasteson, 1975;Lenoir and Honegger, 1983;McMorris et al, 1986). More recent studies have shown that IGF II can be detected in human cerebrospinal fluid (Haselbacher and Humbel, 1982) and brain tissues (Haselbacher et al, 1985).…”

mentioning

confidence: 99%

Characterization of somatomedin/insulin-like growth factor receptors and correlation with biologic action in cultured neonatal rat astroglial cells

Han¹,

Lauder²,

D’Ercole³

1987

J. Neurosci.

107

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The role of somatomedin/insulin-like growth factors (Sm/IGFs) in neural growth and development is not clearly defined. To characterize Sm/IGF receptors and to correlate binding with the biologic actions of Sm/IGFs in a homogeneous population of neural cells, we isolated and studied a nearly pure population of cultured astroglial monolayers derived from cerebral cortices of neonatal rats. Binding of radiolabeled Sm/IGFs was specific, saturable, and reversible, with 90% of the binding occurring within 6 hr of incubation at 4 degrees C. Competitive binding studies with Sm-C/IGF I yielded curvilinear Scatchard plots, while studies with IGF II and multiplication stimulating activity (MSA) yielded linear plots, suggesting that 125I-Sm-C/IGF I binds to more than 1 receptor species, and 125I-IGF II and 125I-MSA bind to one only. These findings were supported by affinity-labeling studies with radiolabeled Sm/IGFs using disuccinimidyl suberate as a cross-linking agent. Sm-C/IGF I appeared to bind to both type I and II Sm/IGF receptors, because cross- linked 125I-Sm-C/IGF I-receptor complexes with molecular weight (Mr) of greater than 300,000 (300K) and 130K (type I receptor) were observed under nonreducing and reducing conditions, respectively, as were 220 and 260K complexes (type II receptor) under the same respective conditions. 125I-IGF II and 125I-MSA, however, bound only to the Mr 220 and 260K moieties under nonreducing and reducing conditions, respectively, suggesting that these peptides bind only to the type II receptor. Competitive binding studies of the cross-linked moieties were consistent with this interpretation. In contrast, 125I-insulin bound poorly to astroglia (less than 0.5% specific binding), and cross- linking studies could not definitely distinguish among low-affinity binding to the type I Sm/IGF receptor, binding to a paucity of insulin receptors, or both. In addition, by combining autoradiography to localize 125I-Sm/IGFs binding on astroglial cells and immunocytochemistry with anti-glial fibrillary acidic protein to identify the cell type, we have demonstrated cell-surface binding and apparent internalization of radiolabeled Sm/IGFs. Concurrent studies of Sm/IGF stimulation of 3H-thymidine incorporation revealed that these cells were most sensitive to Sm-C/IGF I, followed by IGF II and MSA, and insulin. MSA and IGF II, however, were the most potent followed by Sm-C/IGF I and then insulin. Half-maximal stimulations of 3H-thymidine incorporation corresponded closely with half-maximal binding displacement for Sm-C/IGF I and less so for IGF II and MSA.(ABSTRACT TRUNCATED AT 400 WORDS)

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Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures

Cited by 234 publications

References 31 publications

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

Insulin-like growth factor I in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase.

Activity in fetal bovine serum that stimulates erythroid colony formation in fetal mouse livers is insulinlike growth factor I.

Characterization of somatomedin/insulin-like growth factor receptors and correlation with biologic action in cultured neonatal rat astroglial cells

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