Axonal Transport of Endogenous Nerve Growth Factor (NGF) and NGF Receptor in Experimental Diabetic Neuropathy

beta-Nerve growth factor (NGF) is expressed in spermatogenic cells and has testosterone-downregulated low-affinity receptors on Sertoli cells suggesting a paracrine role in the regulation of spermatogenesis. An analysis of the stage-specific expression of NGF and its low affinity receptor during the cycle of the seminiferous epithelium in the rat revealed NGF mRNA and protein at all stages of the cycle. Tyrosine kinase receptor (trk) mRNA encoding an essential component of the high-affinity NGF receptor was also present at all stages. In contrast, expression of low affinity NGF receptor mRNA was only found in stages VIIcd and VIII of the cycle, the sites of onset of meiosis. The low-affinity NGF receptor protein was present in the plasma membrane of the apical Sertoli cell processes as well as in the basal plasma membrane of these cells at stages VIIcd to XI. NGF was shown to stimulate in vitro DNA synthesis of seminiferous tubule segments with preleptotene spermatocytes at the onset of meiosis while other segments remained nonresponsive. We conclude that NGF is a meiotic growth factor that acts through Sertoli cells.

Download Full-text

CRK protein binds to two guanine nucleotide-releasing proteins for the Ras family and modulates nerve growth factor-induced activation of Ras in PC12 cells

Molecular and Cellular Biology ◽

10.1128/mcb.14.8.5495-5500.1994 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5495-5500

Author(s):

M Matsuda ◽

Y Hashimoto ◽

K Muroya ◽

H Hasegawa ◽

T Kurata ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Sh2 Domain ◽

Single Amino Acid ◽

Guanine Nucleotide ◽

Nerve Growth ◽

Tyrosine Residues ◽

Ngf Receptor ◽

Ras Family

It has been reported that growth factors activate Ras through a complex of an adaptor type SH2-containing molecule, Grb2, and a Ras guanine nucleotide-releasing protein (GNRP), mSos. We report on the involvement of another adaptor molecule, CRK, in the activation of Ras. Overexpression of wild-type CRK proteins CRK-I and CRK-II enhanced the nerve growth factor (NGF)-induced activation of Ras in PC12 cells, although the basal level of GTP-bound active Ras was not altered. In contrast, mutants with a single amino acid substitution in either the SH2 or SH3 domain of the CRK-I protein inhibited the NGF-induced activation of Ras. Two GNRPs for the Ras family, mSos and C3G, were coimmunoprecipitated with the endogenous Crk proteins in PC12 cells. The association between C3G and the CRK mutants was dependent upon the presence of intact SH3. The SH2 domain of CRK bound to the SHC protein phosphorylated on tyrosine residues by NGF stimulation. The results demonstrate that, in addition to Grb2, CRK participates in signaling from the NGF receptor and that two GNRPs appear to transmit signals from these adaptor molecules to Ras.

Download Full-text

Nerve growth factor (NGF) in the rat CNS: Absence of specific retrograde axonal transport and tyrosine hydroxylase induction in locus coeruleus and substantia nigra

Brain Research ◽

10.1016/0006-8993(79)90303-2 ◽

1979 ◽

Vol 168 (3) ◽

pp. 473-483 ◽

Cited By ~ 335

Author(s):

M.E. Schwab ◽

U. Otten ◽

Y. Agid ◽

H. Thoenen

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Tyrosine Hydroxylase ◽

Substantia Nigra ◽

Locus Coeruleus ◽

Axonal Transport ◽

Retrograde Axonal Transport ◽

Nerve Growth ◽

Tyrosine Hydroxylase Induction ◽

Rat Cns

Download Full-text

The Changes of Nerve Growth Factor Serum Levels After External Muscle Stimulation and The Correlation with Diabetic Neuropathy Symptom in Diabetic Peripheral Neuropathy

Indonesian Journal of Physical Medicine & Rehabilitation ◽

10.36803/ijpmr.v6i01.146 ◽

2017 ◽

Vol 6 (01) ◽

pp. 7

Author(s):

Dian Herdiansyah ◽

Marina Annete Moeliono ◽

Tertianto Prabowo

Keyword(s):

Nerve Growth Factor ◽

Peripheral Neuropathy ◽

Growth Factor ◽

Diabetic Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Significant Negative Correlation ◽

Muscle Stimulation ◽

Study Objective ◽

Nerve Growth ◽

Before And After

Background: Diabetic Peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Recentstudies have demonstrated the involvement of Nerve growth factor (NGF) in the occurrence of DPN. TheDiabetes Mellitus was caused reduced the number and disruption of the function of the NGF. External MuscleStimulation (EMS) might be induced the NGF synthesis. The study objective has to found the effect of EMSon the NGF.Methods: Study design was before and after treatment without control on subjects with DPN. The bloodsample was taken before and after an intervention, as well as the Diabetic Neuropathy symptom (DNSym) andscore (DNSc). The EMS treated all of the participants within three times a week for four weeks.Results: There were 35 subjects were participated. Paired t-test showed a significant increase in NGF serumlevels and decrease both DNSym and DNSc with the difference value 12.64 ± 16.09 (p=0.000), 1.23 ± 0.82(p=0.000), 1.20 ± 0.85 (p=0.000). There was a significant negative correlation between NGF serum level withthe DNS- INA (r= -0.56; p=0.001) and the DNE-INA (r= -0.48; p=0.007).Conclusion: EMS treatment can increase serum NGF level. EMS has a strong correlation with a decrease inthe value of the DNS-INA and DNE-INA.Keywords: Diabetic Peripheral neuropathy, External Muscle Stimulation, Nerve Growth Factor.

Download Full-text