Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence suggests that insulin-like growth factor-I (IGF-I) acts as a neurotrophic factor in the injured CNS. The role of the related peptide IGF-II is unclear. Therefore, we compared the induction of IGF-II in the developing rat brain following mild or severe hypoxic-ischemic (HI) injuries. Ligation of the right carotid artery of 21 day old rats followed by either 15 or 60 min exposure to 8% oxygen led to mild or severe unilateral damage respectively. Brains were collected at 1 day, 3, 5, 7 and 10 days, post-hypoxia. In situ hybridization showed that the 15 min injury (which produced selective neuronal loss) produced no change in basal IGF-II gene expression. However, the 60 min injury, which resulted in cortical infarction and severe neuronal loss in other regions, led to the induction of IGF-II mRNA mainly in the infarcted cortex, from 5-7 days post-hypoxia. Immunohistochemical analysis of brains collected 10 days after the 60 min injury showed that IGF-II immunoreactivity (IR) was also increased, predominantly in damaged regions, but also in the contralateral hippocampus. IGF-II IR was associated with non-neuronal cells that appeared to be microglial-like cells and astrocytes. Together these data suggest that IGF-II may modulate the response of glial cells during recovery from cerebral infarction.
Brain Res Mol Brain Res 1995 Mar
PMID:Insulin-like growth factor II is induced during wound repair following hypoxic-ischemic injury in the developing rat brain. 777 4

Glial cell-line derived neurotrophic factor (GDNF) has recently been cloned and shown to have trophic effects on dopaminergic nigral neurons. However, GDNF mRNA has not been detected in striatum or other forebrain areas of adult rat. Using limbic motor status epilepticus induced by pilocarpine to activate neurons in motor and limbic areas, we now demonstrate GDNF mRNA signals in the striatum, hippocampus and cortex using in situ hybridisation. The finding of GDNF mRNA in the stimulated striatum opens the possibility that GDNF may be a target-derived, trophic factor in the nigro-striatal system. This expression of GDNF mRNA may be linked to excitatory cortical input. Increases in GDNF mRNA after status epilepticus in hippocampus and neocortex indicate additional roles for GDNF.
Brain Res Mol Brain Res 1994 Oct
PMID:Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status epilepticus in rats. 785 63

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two structurally-related neurotrophins synthesized in dentate gyrus granule cells and pyramidal neurons of the hippocampal formation. These neurons receive excitatory glutamatergic afferents from the entorhinal cortex via the angular bundle/perforant path. In the present study, we tested whether electrophysiological stimulation of this glutamatergic pathway modifies NGF or BDNF messenger RNA (mRNA) expression in vivo. Within hours following brief trains of high frequency angular bundle stimulation, the levels of mRNA encoding both neurotrophins were increased exclusively in granule cells of the ipsilateral dentate gyrus. The increase in neurotrophic factor mRNA expression was found to be mediated through the N-methyl-D-aspartate (NMDA) glutamate receptor subtype, and occurred in the absence of seizure. These findings provide evidence that neurotrophic factor mRNA levels in the hippocampal formation are increased by direct activation of excitatory afferents originating in the entorhinal cortex. We suggest that the function of some neurotrophin-responsive neuronal populations may depend upon the integrity and activity of neurons in the entorhinal cortex, a population of neurons reported to be compromised in patients with Alzheimer's disease.
Brain Res Mol Brain Res 1994 Apr
PMID:Neurotrophic factor mRNA expression in dentate gyrus is increased following in vivo stimulation of the angular bundle. 791 2

A unilateral hypoxia-ischaemia (HI) 21-day-old rat preparation was used to assess the effects of HI on the expression of the immediate-early gene proteins (IEGPs) c-Fos/FRAs, Fos B, c-Jun, Jun B, Jun D, Krox 20, Krox 24, and on the mRNA for the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Moderate HI (15 min hypoxia) produced delayed, selective neuronal death and was associated with a rapid induction of c-Fos, Fos B, Jun B, Jun D, and c-Jun proteins, but not Krox 20 protein or BDNF mRNA, in neurons on the side of HI and also a delayed expression of c-Jun (and to a lesser extent c-Fos/FRA's and Fos B) 24-48 h after HI in neurons that underwent delayed neuronal death. Krox 24 showed an initial induction followed by a long-lasting suppression of its expression in regions undergoing cell loss. Severe HI (60 min hypoxia) resulted in seizures and rapid neuronal loss and infarction (necrotic cell death) on the side of HI, and was associated with early induction of c-Fos, Fos B, c-Jun, Jun B, Jun D, Krox 20 and Krox 24 protein and BDNF mRNA in neurons on the non-ligated side of the brain. Fos, c-Jun, Jun B, Jun D and Krox 24, but not Krox 20, Fos B, or BDNF mRNA, were also induced in non-nerve cells on the damaged side of the brain after both moderate and severe HI, and many of these cells appeared to be dividing. Thus, moderate HI induces IEGP's in neurons and non-nerve cells in damaged regions, whereas severe HI induces IEGP's and BDNF in non-damaged regions. c-Jun (and to a lesser extent c-Fos/FRA's) showed a prolonged expression in neurons undergoing delayed, but not necrotic, cell death suggesting that they may be involved in the biochemical cascade that causes selective delayed neuronal death. BDNF was not induced by HI, and therefore, does not appear to play an endogenous neuroprotective role in the CNS.
Brain Res Mol Brain Res 1994 Aug
PMID:Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain. 798 48

In a previous report we demonstrated that basic fibroblast growth factor (bFGF), as a multipotent neurotrophic factor, could prevent retrograde degeneration of the thalamic neurons after ablation of the somatosensory cortex. To elucidate the mechanism of this bFGF action, we examined changes in FGF receptor (FGFR) mRNA (flg) expression with in situ hybridization. The FGF receptor protein was detected with the immunoblotting method. The FGFR mRNA expression was found to be diffusely increased in the affected cortex. Microscopic observation indicated that FGFR mRNA was expressed in several types of cortical cells including neurons and non-neuronal cells. This increase could be observed as early as 6 hours after surgery and lasted for 48 hours. In the thalamus, however no change in FGFR mRNA signals was observed. Western blotting detected a protein immunoreactive to anti-FGFR antibody. Samples from the periablated cortex showed an increase in FGFR protein. Samples from the thalamus, however, showed no difference in FGFR protein level between the lesion side and the contralateral side. Application of exogenous bFGF in Gelfoam to the cortical ablation cavity did not show any effect on the gene expression or protein level of FGFR. These results suggest that FGFR is diffusely induced throughout the injured cortex in the early phase after injury and that bFGF may play an important role after injury. Topically applied bFGF might thus modulate cellular responses in the cortex and have a neurotrophic effect on the affected thalamic neurons.
Brain Res Mol Brain Res 1994 Aug
PMID:Messenger RNA and protein expression of basic fibroblast growth factor receptor after cortical ablation. 798 51

Crystals of a bovine neurotrophic factor S100 beta with and without Ca2+ bound has been crystallized by vapor diffusion from solutions of polyethylene glycol. The crystals of S100 beta with Ca2+ bound were monoclinic and belong to space group P21 with unit cell dimensions a = 36.2 A, b = 55.63 A, c = 48.39 A and beta = 111.77 degrees. The asymmetric unit contains two molecules (one dimer) which exhibit an approximate 222 point symmetry. The crystals of apo-S100 beta were tetragonal and belong to space group P4(1) with unit cell dimensions a = b = 56.04 A, c = 111.7 A. The asymmetric unit contains four molecules (two dimers) which exhibit 422 point symmetry. Both these crystal forms diffract to greater than 1.9 A resolution.
J Mol Biol 1994 Feb 25
PMID:Crystallization and preliminary X-ray analysis of apo-S100 beta and S100 beta with Ca2+. 811 5

A new classificational method based on the availability of peptide fragments unique for a certain protein family is presented. Seven common peptide fragments unique for the nerve growth factor amino acid sequence are determined, and two of them are found in the neurotrophic factor from pig brain.
Mol Biol (Mosk)
PMID:[Determination of unique peptide fragments in nerve growth factors]. 814 49

Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide which acts at the epidermal growth factor receptor to produce its biologic effects. Recent studies have demonstrated that TGF alpha may act as a neurotrophic factor. Cerebral hemispherectomy (hemidecortication) is performed on some children with intractable epilepsy. Prior studies have demonstrated improved functional recovery in both children and animals when the surgery is performed at a very early age. In order to test whether TGF alpha may be involved in the functional recovery of the neostriatum following cerebral hemidecortication, we performed in situ hybridization for TGF alpha mRNA on brains of rats which underwent hemispherectomy at postnatal day (P) 6 or P12 or in adulthood, and sacrificed one, 7, or 30 days following surgery. Normal striatal expression in control animals was very high at P6 and then decreased throughout development. In animals undergoing lesion at earlier ages (P6 and P12), TGF alpha mRNA expression was first depressed in the ipsilateral neostriatum one day after surgery and then elevated to supranormal levels 7 and 30 days after surgery. Maximal decreases (40% below contralateral neostriatum) were seen in animals lesioned at P12 and sacrificed the next day. Maximal elevations (60% greater than opposite neostriatum) were seen in animals operated on at P6 and sacrificed 30 days post surgery. Expression in the adult animal was only mildly affected, with a 20% increase found in the ipsilateral caudate 7 days after the lesion, but no significant changes after one or 30 days survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1994 Jan
PMID:Cerebral hemidecortication alters expression of transforming growth factor alpha mRNA in the neostriatum of developing rats. 816 11

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are two neurotrophic factors that play a role in neuronal maintenance and repair. The identification and characterization of mechanisms regulating neurotrophic factor availability in the central nervous system are vital to the development of therapeutic tools for prevention of neuronal degeneration. The lipophilic beta-adrenergic receptor (BAR) agonist clenbuterol was used to assess whether activation of central BAR changes the levels of NGF and bFGF mRNA. Within 5 hr, clenbuterol (10 mg/kg, intraperitoneally) elicited a 2-3-fold increase in bFGF and NGF mRNA content in rat cerebral cortex. The induction of bFGF and NGF mRNA expression showed anatomical specificity. Among the various brain areas examined, bFGF mRNA levels were increased in the cerebral cortex, hippocampus, and cerebellum, whereas induction of NGF mRNA was observed only in the cerebral cortex. Isoproterenol, a BAR agonist that does not cross the blood-brain barrier, also elicited a 2-3-fold increase in bFGF and NGF mRNA in the cerebral cortex. Propranolol (5 mg/kg, intraperitoneally), a lipophilic BAR antagonist, blocked the induction of NGF and bFGF mRNA mediated by either isoproterenol or clenbuterol, whereas nadolol (5 mg/kg, intraperitoneally), a BAR antagonist that does not cross the blood-brain barrier, blocked only the effect of isoproterenol. Therefore, activation of both central and peripheral BAR play a role in the regulation of bFGF and NGF mRNA expression. Moreover, in adrenalectomized rats, isoproterenol failed to increase bFGF and NGF mRNA, whereas clenbuterol elicited a 2-fold increase in bFGF mRNA in the cortex and hippocampus. Our data suggest that both adrenal steroids and noradrenaline might regulate the availability of selective neurotrophic factors in the adult central nervous system.
Mol Pharmacol 1993 Feb
PMID:Regulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and adrenal steroids in rat central nervous system. 838 5

The present study was undertaken to investigate the regulatory mechanisms of fibroblast growth factor-1 and -2 (FGF-1 and FGF-2) gene expression compared with ciliary neurotropic factor (CNTF) in rat cortical astrocytes. Glial cells represent a source of different trophic factors and cytokines that can influence the survival of multiple cell populations within the central nervous system. We found that the beta-adrenergic receptor agonist (betaAR) isoproterenol produced a significant induction of FGF-2 gene expression and protein in type I astrocytes. On the contrary, the gene expression for FGF-1 and CNTF is markedly reduced after exposure to isoproterenol. The changes produced by the beta AR agonist is mimicked by cyclic AMP analogues (8-bromo-cAMP) or 3-isobutyl-1-methyl-xanthine, a cAMP phosphodiesterase inhibitor, which indicates that intracellular elevation of this second messenger is responsible for these effects. The regulation of neurotrophic factors by isoproterenol is not restricted to cortical astrocytes and may take place through different mechanisms. Inhibition of protein synthesis prevents the decrease in CNTF without affecting the changes in FGF-1 and FGF-2 gene expression. Coincubation of isoproterenol with actinomycin D, an inhibitor of gene transcription, prevents the modification of neurotrophic factor biosynthesis, indicating that transcriptional mechanisms are indeed involved in these regulatory pathways. However, the determination of FGF-2 mRNA half-life suggests that the effect of the betaAR agonist can be in part the result of mRNA stabilization. The mechanisms that we describe can be important in the maintenance of neuronal homeostasis and may be relevant in the development of alternative strategies for the treatment of acute and chronic neurodegenerative disorders
Mol Pharmacol 1996 Apr
PMID:Cyclic AMP-dependent regulation of fibroblast growth factor-2 messenger RNA levels in rat cortical astrocytes: comparison with fibroblast growth factor-1 and ciliary neurotrophic factor. 860 99


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