PubMed · 8931264
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A J Harmar, A D Ogilvie. 1996. Function and dysfunction in the nervous system.. https://doi.org/10.1016/s0166-2236(96)30014-3
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Prothrombin, thrombin receptor (ThR), and protease nexin-1 (PN-1) mRNA levels in mouse muscle were quantified using competitive reverse transcriptase-polymerase chain reaction during development and after denervation to examine the possible role of thrombin in activity-dependent synapse elimination at the neuromuscular junction. The results showed that the levels of prothrombin and ThR were maximal at birth and decreased by two orders of magnitude by postnatal day 20 (P20). The level of PN-1 mRNA was fairly constant during development except for a 4-fold to 5-fold downregulation at P10 and P15, the periods of maximal synapse elimination at the rodent neuromuscular junction. The expression of prothrombin mRNA in muscle at birth was 41-fold and 22-fold lower than those of ThR and PN-1, respectively, and the level of difference between prothrombin and PN-1 reached almost three orders of magnitude at adulthood. Denervation of adult muscle resulted in a reversal of the relative expression levels of the three genes. There were rapid 8-fold and 10-fold increases in prothrombin and ThR mRNA, respectively, and a 2-fold decrease in PN-1 mRNA. The changes in mRNA levels of the three genes after denervation indicated that these genes were regulated in a innervation-dependent manner and that nerve activity may play an important regulatory role in the expression of prothrombin, ThR, and PN-1. The concurrent regulation of prothrombin and ThR suggests that thrombin-mediated cellular activities in muscle may be affected via the activation of ThR. An elevated level of local thrombin or thrombin-like activity might result from the decreased inhibitory activity of PN-1 during the period of peak synapse elimination in muscle development.
A unilateral hypoxic-ischemic (HI) episode in immature rat brain was used to investigate the role of the immediate early genes c-fos and c-jun in delayed neuronal death and survival. This HI paradigm results in an apoptotic cell death in selectively vulnerable areas, in particular the hippocampal CA1 pyramidal cell layer. In susceptible regions undergoing delayed neuronal death there was a prolonged induction of both c-Jun and c-Fos (mRNA and protein). This expression occurred in parallel with a pronounced increase in AP-1 DNA binding activity but was not associated with either increased levels of Jun NH2-terminal kinase or phosphorylation of c-Jun (ser-63). In addition to changes in immediate early gene expression, the CA1 neurons showed a delayed increase in the expression of amyloid precursor protein (APP751) mRNA, suggesting that APP, which contains an AP-1 site, might be a down-stream gene regulated by the Jun transcription factor in neurons dying by apoptosis. The surviving dentate granule cells also showed an increase in Fos, Jun, and APP751 although this expression occurred earlier than in the CA1 neurons and declined rapidly. These results are discussed with respect to the role of these proteins in neuronal death and survival.
The amyloid beta-protein (Abeta) is the major proteinaceous component of the amyloid deposits that accumulate extracellularly in the brain of Alzheimer's disease (AD). Abeta is generated proteolytically from a larger beta-amyloid precursor protein (betaAPP). The apparent overexpression of the betaAPP gene in certain areas of AD brains indicate that abnormalities in gene regulation might be an important factor in AD. Here, I report that an upstream regulatory element (URE) located between -2257 to -2234 base pair (bp) of the human betaAPP promoter may interact with a novel protein(s) as determined by a gel shift assay. To determine whether this novel protein is related to an already characterized transcription factor, a gel shift assay was performed using various specific competitors in human neuroblastoma and rat pheochromocytoma (PC12) cells. The labeled URE probe could interact with a distinct nuclear factor which was not competed by the oligonucleotides specific for the different transcription factors, AP1, AP2, AP3, GRE, Oct1, NF1 and NF-kappaB. Alternatively the specific protein band(s) detected with either the labeled NF-kappaB or NF1 probe could not be competed out with an excess of unlabeled URE. To determine if such a band could be detected in human brain tissue samples, a gel shift assay from the nuclear extracts of the human brain was performed. A distinct URE-specific nuclear factor was detected in different regions of the brain as well. To determine the size of the protein(s) that were specifically bound in the DNA-protein complexes, Southwestern blotting was performed. Using the URE probe, two major protein bands of approximately 53 and 116 kDa were detected in PC12 nuclear extracts. These results suggest that the protein factor(s) interacting with URE is not related to the known transcription factors tested, and that the protein is expressed in certain cell types and different regions of the human brain.