Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize neuronal gene expression in amyotrophic lateral sclerosis (ALS), we quantitated one glial and three neuronal mRNAs in spinal cords of 7 subjects with ALS and 11 controls. The ALS cases showed no loss of mRNA for the neurofilament light subunit when assessed with in situ hybridization. Northern analysis, and RNase protection assay; and no loss of mRNA for amyloid precursor protein or a growth-associated protein (GAP-43/B-50) on Northern analysis. ALS cords also showed no significant change in glial mRNA. Our findings indicate that expression of these neuronal mRNAs is well maintained in ALS-afflicted spinal cord. They do not support the hypothesis of a generalized impairment of neuronal gene transcription in the pathogenesis of this disorder.
 ...
PMID:Neuronal gene expression in amyotrophic lateral sclerosis. 215 97

SCG10 is a developmentally regulated, growth-associated protein (GAP) that was isolated as a neuronal marker of the neural crest. It was recently found that SCG10 shares an amino acid sequence similarity with a phosphoprotein named stathmin or p19 of which phosphorylation is induced by nerve growth factor and vasoactive intestinal peptide in PC12 cells and striatal neurons, respectively. While expression of SCG10 messenger RNA dramatically decreases during postnatal development, significant levels of expression still persist into adulthood. To examine possible roles of SCG10 in the adult brain, we examined the distribution of messenger RNAs encoding SCG10 and p19/stathmin as well as GAP-43 in adult rat brain sections by northern blot, RNase protection and in situ hybridization. SCG10 transcripts are found at high levels in long-distance projecting neurons and neurons with extensive dendritic arbors, while p19/stathmin messenger RNA was weakly distributed over most brain areas. Both messenger RNAs are expressed in neuronal subpopulations but not in glia, although the overall distribution of the transcripts of these two structurally related genes is distinct. The spatial and temporal expression profiles of SCG10 messenger RNA is comparable to that of GAP-43, another neuronal GAP, in the developing nervous system, however the expression of SCG10 messenger RNA in the adult brain is distinct from that of GAP-43, especially in the hippocampus and brain stem, where the dentate granule cells and sensory and motor neurons of brainstem express SCG10 but not GAP-43. These results suggest that SCG10 may have a unique role in the neuronal growth-response of subsets of mature neurons, and that SCG10 plays a stathmin-like function at nerve terminals, to which it may be rapidly transported by means of membrane attachment due to a hydrophobic domain present in SCG10 but not in p19/stathmin. This suggests that SCG10 may play a role in structural plasticity in the adult brain.
 ...
PMID:Differential localization of SCG10 and p19/stathmin messenger RNAs in adult rat brain indicates distinct roles for these growth-associated proteins. 793 11

Two new oligonucleotide anti-sense probes and their corresponding sense probes specific for mouse GAP-43 mRNA were synthesized and end-labelled with digoxygenin. They were used to localize GAP-43 mRNA in the spinal cords of normal mice and in mice 3 and 7 days following unilateral sciatic nerve cut. GAP-43 mRNA was found to be expressed at low levels in motor and other neurons of the normal spinal cords. As expected from other studies, up-regulation occurred in the cell bodies of axotomized motor neurons but, in addition, up-regulation was also observed in the cell bodies of intact motor neurons contralateral to the lesion. Densitometer measurements showed that the up-regulation of GAP-43 mRNA was less in the intact, contralateral motor neuron cell bodies than in the axotomized motor neuron cell bodies and furthermore was transient, being higher at 3 days than at 7 days following axotomy. Both anti-sense probes gave the same result, although differences in cellular localization was observed, and the two sense probes were negative. Probe binding was abolished by pretreatment of the sections with ribonuclease and hybridization was carried out under different conditions of stringency in order to ascertain whether the contralateral expression of GAP-43 mRNA was a true reflection of its distribution in vivo. There is conflicting evidence on the presence or absence of contralateral effects following unilateral peripheral nerve injury in the literature, and it is suggested that these differences can be accounted for by the methodology and type of probe used.
 ...
PMID:Expression of GAP-43 mRNA in mouse spinal cord following unilateral peripheral nerve damage: is there a contralateral effect? 812 18

Schizophrenia has been associated with anatomical and functional abnormalities of the dorsolateral prefrontal cortex (DLPFC), which may reflect abnormal connections of DLPFC neurons. We measured mRNA levels of growth-associated protein (GAP-43), a peptide linked to the modifiability of neuronal connections, in post-mortem brain tissue from two cohorts of patients with schizophrenia and controls. Using the RNase protection assay (RPA), we found a significant reduction in GAP-43 mRNA in the DLPFC, but not in the hippocampus, of patients with schizophrenia. With in situ hybridization histo- chemistry (ISHH), performed on a separate cohort, we confirmed the reduction of GAP-43 mRNA in the DLPFC of patients with schizophrenia. We detected reduced GAP-43 mRNA per neuron in layers III, V and VI of patients with schizophrenia compared with normal controls and patients with bipolar disorder. Thus, glutamate neurons in DLPFC of schizophrenic patients may synthesize less GAP-43, which could reflect fewer and/or less modifiable connections than those in normal human brain, and which may be consistent with the deficits of prefrontal cortical function that characterize schizophrenia.
 ...
PMID:Reduced GAP-43 mRNA in dorsolateral prefrontal cortex of patients with schizophrenia. 1120 68

We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area surrounding the lesioned tissue, along with signs of increased oxidative stress and apoptosis. There was also significant upregulation of cytokines/growth factors such as tumor necrosis factor-alpha, interleukin (IL)-1 alpha/beta, and IL-6 as measured by ribonuclease protection assay. Mt3-null mice did not differ from control mice in these responses, in sharp contrast to results obtained in Mt1- Mt2-null mice. In contrast, Mt3-null mice showed increased expression of several neurotrophins as well as of the neuronal sprouting factor GAP-43. Thus, unlike MT-I and MT-II, MT-III does not affect the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process.
 ...
PMID:Role of metallothionein-III following central nervous system damage. 1275 64

Phorbol ester treatment of human SH-SY5Y neuroblastoma cells, which leads to mature neuron-like cells with a sympathetic phenotype, induces outgrowth of neurites which are terminated by growth cones. The neurite extension is parallelled by an increased expression of the growth-associated protein, GAP-43. At the mRNA level, two GAP-43 mRNA species of 1.4 and 1.6 kb, respectively, were detected in SH-SY5Y cells. Both the low- and high-molecular-weight GAP-43 transcripts cosedimented with a polysomal fraction, indicating translation of both types of transcripts. To structurally characterize these GAP-43 mRNAs, several cDNA clones were isolated. The only difference identified corresponded to various size extensions in the 5'-untranslated region. A human genomic DNA fragment extending 1145 bp 5' of the GAP-43 translation start site, including a putative promoter region of the GAP-43 gene, was also characterized. Comparison of human and rat GAP-43 genomic sequences revealed an 85% identity between the first 900 bp 5' of translation start site. By RNase protection analysis, two clusters of putative transcription start sites, located approximately 200 bp apart, were identified. DNaseI footprinting analyses, using nuclear extracts prepared from untreated and TPA-treated SH-SY5Y cells, revealed specific footprints primarily detected in extracts prepared from differentiating cells. These clustered at positions immediately 5' of the two putative transcription start site regions. GAP-43 mRNA expression was finally studied using a probe which specifically recognizes the high-molecular-weight GAP-43 transcripts. Five tested human neuroblastoma cell lines and human fetal brain tissue expressed these transcripts. Furthermore, during differentiation of SH-SY5Y and LA-N-5 cells, both sizes of GAP-43 transcripts were transiently induced with the larger slightly preceeding the smaller mRNA species.
 ...
PMID:Human GAP-43 Gene Expression: Multiple Start Sites for Initiation of Transcription in Differentiating Human Neuroblastoma Cells. 1991 63