Nerve growth factor as a paradigm for other polypeptide growth factors

Ethanol ingestion by pregnant women is the primary cause of fetal alcohol syndrome, which is characterized by brain abnormalities and decreased mental capacity. In the present study,cultured neurons from embryonic rat cortices were used to study the effects of ethanol on cell survival and the potential for neuroprotection by certain growth factors and estrogen. Neurons were grown in the presence of a glial plane and in the absence of serum. Survival was assessed following chronic treatment with ethanol (45 mM) in the presence and absence of either nerve growth factor (NGF, 100ng/ml), basic fibroblast growth factor (bFGF, 5ng/ml), insulin-like growth factor I or II (IGF-I, IGF-II, both 10ng/ml), or estrogen (Es, 10nM) added on days one and four in vitro. On day in vitro 4 (DIV4) ethanol effects on neuronal viability were significantly prevented by NGF, bFGF, IGF-I, and Es. DIV6 survival of ethanol-treated neurons was increased significantly by treatment with NGF, bFGF, IGF-I, IGF-II, and Es. Nerve growth factor, bFGF, and IGF-I effects were shown to be dose-dependent. Administration of 1-100 ng/ml NGF, 0.05-5 ng/ml bFGF and 0.1-10ng/ml IGF-I led to statistically significant effects at 10, 5, and 1 ng/ml, respectively. Thus, ethanol’s effect on neuronal survival may be inhibited by simultaneous treatment with physiological doses of these factors.

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Nerve growth factor regulates gene expression by several distinct mechanisms

Molecular and Cellular Biology ◽

10.1128/mcb.9.1.135-143.1989 ◽

1989 ◽

Vol 9 (1) ◽

pp. 135-143

Author(s):

K O Cho ◽

W C Skarnes ◽

B Minsk ◽

S Palmieri ◽

L Jackson-Grusby ◽

...

Keyword(s):

Gene Expression ◽

Growth Factors ◽

Nerve Growth Factor ◽

Growth Factor ◽

Cholera Toxin ◽

Phorbol Myristate Acetate ◽

Kinase Inhibitor ◽

Transcriptional Level ◽

Myristate Acetate ◽

Nerve Growth

To help elucidate the mechanisms by which nerve growth factor (NGF) regulates gene expression, we have identified and studied four genes (a-2, d-2, d-4, and d-5) that are positively regulated by NGF in PC12 cells, including one (d-2) which has previously been identified as a putative transcription factor (NGF I-A). Three of these genes, including d-2, were induced very rapidly at the transcriptional level, but the relative time courses of transcription and mRNA accumulation of each of these three genes were distinct. The fourth gene (d-4) displayed no apparent increase in transcription that corresponded to the increase in its mRNA, suggesting that NGF may regulate its expression at a posttranscriptional level. Thus, NGF positively regulates gene expression by more than one mechanism. These genes could also be distinguished on the basis of their response to cyclic AMP. The expression of d-2 and a-2 was increased by cholera toxin and further augmented by NGF; however, cholera toxin not only failed to increase the levels of d-5 and d-4 mRNA but also actually inhibited the NGF-dependent increase. The expression of each of these genes, including d-2 (NGF I-A), was also increased by fibroblast growth factor, epidermal growth factor (EGF), phorbol myristate acetate, and in some cases insulin, showing that the regulation of these genes is not unique to NGF. Because each of these genes was expressed in response to phorbol myristate acetate and EGF, their expression may be necessary but is certainly not sufficient for neurite formation. The protein kinase inhibitor K-252a prevented the NGF-associated, but not the acidic FGF-associated, induction of d-2 and d-5 gene expression, suggesting that these two growth factors may regulate gene expression via different cellular pathways. The study of the regulation of the expression of these and other NGF-inducible genes should valuable new information concerning how NGF and other growth factors cause neural differentiation.

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The Role of Zinc on the Trophic Growth Factors, Nerve Growth Factor and Gustin

Trace Elements in Man and Animals 6 ◽

10.1007/978-1-4613-0723-5_130 ◽

1988 ◽

pp. 385-387 ◽

Cited By ~ 2

Author(s):

R. I. Henkin ◽

J. S. Law ◽

N. R. Nelson

Keyword(s):

Growth Factors ◽

Nerve Growth Factor ◽

Growth Factor ◽

Nerve Growth

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THE EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 AND NERVE GROWTH FACTOR ON DENERVATED MUSCLE ATROPHY

Journal of Musculoskeletal Research ◽

10.1142/s0218957701000568 ◽

2001 ◽

Vol 05 (03) ◽

pp. 193-203 ◽

Cited By ~ 1

Author(s):

Boonsin Buranapanitkit ◽

Zhuqing Qu ◽

Morey M. Moreland ◽

Alan Geater ◽

George Somogyi ◽

...

Keyword(s):

Growth Factors ◽

Nerve Growth Factor ◽

Growth Factor ◽

Muscle Atrophy ◽

Interstitial Fibrosis ◽

Insulin Like Growth Factor ◽

Denervated Muscle ◽

Nerve Growth ◽

Wet Weight ◽

The Mean

The effects of growth factors on denervated muscle atrophy in mouse gastrocnemius muscle were studied by morphometric, physiologic and histologic methods. Fifteen mice were randomized into three groups: intact, denervated-insulin-like growth factor-1-treated (D-IGF-1) and denervated-nerve growth factor-treated (D-NGF). In denervated animals, the left sides were used as a control by injecting balanced salt solution (HBSS), while the right sides were injected with growth factors. The mean wet weight and the mean wet weight/body weight were significantly higher in D-IGF-1 muscles compared to the D-NGF and D-HBSS muscles, but were not different from the muscle of intact controls. Physiologic testing showed that the mean maximal tetanic twitch strength and the mean maximal fast twitch strength were also significantly higher in the D-IGF-1 muscles than in the D-NGF and D-HBSS muscles. Mean time-to-peak was significantly only decreased in the D-NGF muscles. Histological studies found that the mean percentage of type 2 fiber was significantly higher in D-NGF muscles. The types I and II mean diameters in the D-IGF-1 muscles were larger than in the D-NGF and D-HBSS muscles, but all denervated muscles had higher interstitial fibrosis than the intact controls. In conclusion, we show that IGF-1 can effectively retard denervated muscle atrophy by increasing types I and II fibre muscle diameter. However, IGF-1 cannot prevent interstitial fibrosis in the denervated muscle.

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Role of Tyrosine Kinase Receptors in Angiotensin II AT2 Receptor Signaling: Involvement in Neurite Outgrowth and in p42/p44mapk Activation in NG108-15 Cells

Endocrinology ◽

10.1210/en.2005-1315 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4646-4654 ◽

Cited By ~ 31

Author(s):

Bianca Plouffe ◽

Marie-Odile Guimond ◽

Hélène Beaudry ◽

Nicole Gallo-Payet

Keyword(s):

Growth Factors ◽

Nerve Growth Factor ◽

Angiotensin Ii ◽

Growth Factor ◽

Neurite Outgrowth ◽

Egf Receptor ◽

Growth Factor Receptor ◽

At2 Receptor ◽

Ang Ii ◽

Nerve Growth

NG108–15 cells, which have a rounding-up morphology when cultured in serum-supplemented medium, extend neurites when stimulated for 3 d with angiotensin II (Ang II). The aim of the present study was to investigate whether growth factor receptors are necessary for mediating the effects of Ang II. A 3-d treatment with AG879, an inhibitor of nerve growth factor receptor TrkA, strongly affected neurite outgrowth and phosphorylation of p42/p44mapk induced by Ang II. PD168393, an inhibitor of epidermal growth factor (EGF) receptor slightly decreased Ang II-induced neurite outgrowth, whereas AG213, an inhibitor of both platelet-derived growth factor receptor and EGF receptor, stimulated neurite outgrowth and p42/p44mapk phosphorylation on its own, without affecting further stimulation with Ang II. Moreover, Ang II induced the phosphorylation of TrkA (maximum at 5 min of incubation in the presence of serum or at 20 min in cells depleted in serum for 2 h) and a rapid increase in Rap1 activity, both effects abolished in cells preincubated with 10 μm AG879. In summary, the present results demonstrate that AT2 receptor-induced sustained activation of p42/p44mapk and corresponding neurite outgrowth are mediated by phosphorylation of the nerve growth factor TrkA receptor. However, the results also point out that the presence of other growth factors, such as EGF or PDFG, may interfere with the effect of Ang II. Altogether, the current findings clearly indicate that the effects of the AT2 receptor on neurite outgrowth dynamics are modulated by the presence of growth factors in the culture medium.

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Nerve growth factor regulates HCO 3 − absorption in thick ascending limb: modifying effects of vasopressin

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.4.c931 ◽

1998 ◽

Vol 274 (4) ◽

pp. C931-C939 ◽

Cited By ~ 24

Author(s):

David W. Good ◽

Keyword(s):

Growth Factors ◽

Nerve Growth Factor ◽

Growth Factor ◽

Common Mechanism ◽

Renal Tubules ◽

Thick Ascending Limb ◽

Critical Determinant ◽

Nerve Growth ◽

Exchange Activity

Growth factors stimulate Na+/H+exchange activity in many cell types but their effects on acid secretion via this mechanism in renal tubules are poorly understood. We examined the regulation of [Formula: see text]absorption by nerve growth factor (NGF) in the rat medullary thick ascending limb (MTAL), which absorbs [Formula: see text]via apical membrane Na+/H+exchange. MTAL were perfused in vitro with 25 mM[Formula: see text] solutions (pH 7.4; 290 mosmol/kgH2O). Addition of 0.7 nM NGF to the bath decreased [Formula: see text]absorption from 13.1 ± 1.1 to 9.6 ± 0.8 pmol ⋅ min−1 ⋅ mm−1( P < 0.001). In contrast, with 10−10 M arginine vasopressin (AVP) in the bath, addition of NGF to the bath increased[Formula: see text] absorption from 8.0 ± 1.6 to 12.5 ± 1.3 pmol ⋅ min−1 ⋅ mm−1( P < 0.01). Both effects of NGF were blocked by genistein, consistent with the involvement of tyrosine kinase pathways. However, the AVP-dependent stimulation required activation of protein kinase C (PKC), whereas the inhibition was PKC independent, indicating that the NGF-induced signaling pathways leading to inhibition and stimulation of [Formula: see text]absorption are distinct. Hypertonicity blocked the inhibition but not the AVP-dependent stimulation, suggesting that hypertonicity and NGF may inhibit [Formula: see text] absorption via a common mechanism. These data demonstrate that NGF inhibits[Formula: see text] absorption in the MTAL under basal conditions but stimulates [Formula: see text]absorption in the presence of AVP, effects that are mediated through distinct signal transduction pathways. They also show that AVP is a critical determinant of the response of the MTAL to growth factor stimulation and suggest that NGF can either inhibit or stimulate apical Na+/H+ exchange activity depending on its interactions with other regulatory factors. Locally produced growth factors such as NGF may play a role in regulating renal tubule [Formula: see text] absorption.

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