Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase that is abundantly expressed in several specific areas of the brain, which are exceptionally vulnerable to stroke, epilepsy, and neurodegenerative diseases. In this study, we assessed the effects of high level activity of calcineurin on neuronal cells. Virus-mediated high level constitutive activity of calcineurin rendered neuronal cells susceptible to apoptosis induced by serum reduction or by a brief exposure to calcium ionophore. Adenovirus-mediated, high level forced activity of calcineurin induced cytochrome c/caspase-3-dependent apoptosis in neurons. Preincubation with the calcineurin inhibitors cyclosporin A and FK506 reduced susceptibility to apoptosis. High level constitutive expression of Bcl-2 or CrmA or incubation with a specific caspase-3 inhibitor inhibited the calcineurin-induced apoptosis. These data indicate that high level constitutive activity of calcineurin predisposes neuronal cells to cytochrome c/caspase-3 dependent apoptosis even under sublethal conditions.
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PMID:High level calcineurin activity predisposes neuronal cells to apoptosis. 1056 26

Emerging evidence has shown that tumor suppressor p53 expression is enhanced in response to brain ischemia/hypoxia and that p53 plays a critical role in the cell death pathway in such an acute neurological insult. However the mechanism remains unclear. Recently it was reported that Peg3/Pw1, originally identified as a paternally expressed gene, plays a pivotal role in the p53-mediated cell death pathway in mouse fibroblast cell lines. In this study, we found that Peg3/Pw1 expression is enhanced in peri-ischemic neurons in rat stroke model by in situ hybridization analysis, where p53 expression was also induced by immunohistochemical analysis. Moreover, we found that p53 was co-localized with Peg3/Pw1 in brain ischemia/hypoxia by double staining analysis. In human neuroblastoma-derived SK-N-SH cells, Peg3/Pw1 mRNA expression is enhanced remarkably at 24 h post-hypoxia, when p53 protein expression was also enhanced at high levels. Subcellular localization of Peg3/Pw1 was observed in the nucleus. Adenovirus-mediated high dose p53 overexpression induced Peg3/Pw1 mRNA expression. Overexpression of Peg3/Pw1 reduced cell viability under hypoxic conditions, whereas that of the C-terminal-deleted mutant and anti-sense Peg3/Pw1 inhibited hypoxia-induced cell death. These results suggest that Peg3/Pw1 is involved in the p53-mediated cell death pathway as a downstream effector of p53 in brain ischemia/hypoxia.
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PMID:Peg3/Pw1 is involved in p53-mediated cell death pathway in brain ischemia/hypoxia. 1167 86

Gene therapy may be a promising approach for the treatment of brain ischemia. Because older populations are susceptible to ischemic stroke, we examined the effects of aging on adenovirus-mediated gene transfer to the ischemic brain of rats. Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of aged and adult spontaneously hypertensive rats. Ninety minutes after ischemia, an adenoviral vector encoding beta-galactosidase was injected into the contralateral (C) and ipsilateral [peri-ischemic (I-p) and ischemic core (I-c)] parietal cortices. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry. Transgene expression was scored semiquantitatively as an expression score by histochemistry and also quantitatively analyzed by chemiluminescence assay. Changes in CBF after ischemia in aged rats were not significantly different from those in adult rats, although the infarct rim in the older rats tended to be closer to the midline than in the younger rats. beta-galactosidase was detected in both neurons and non-neuronal cells at C and I-p, and was primarily present in non-neuronal cells at I-c. The expression scores 1 and 4 days after ischemia in the aged rats were similar to those in the adult rats. However, the score for the I-c at 7 days after injection was significantly greater in the older rats than in the younger adult rats. beta-galactosidase activity at I-c 7 days after ischemia in the aged rats (8.0+/-1.7mU/mg protein) was significantly greater than that in the adult rats (1.3+/-0.4, p<0.01). Adenovirus-mediated gene transfer to the ischemic brain may thus be more effective in aged rats than in adult rats.
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PMID:Adenovirus-mediated gene transfer to ischemic brain is augmented in aged rats. 1267 Jun 29

Oxidative stress is considered one of the causative pathomechanisms of nervous system diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke and excitotoxicity. The basal expression of six different peroxiredoxin (Prx) isozymes show distinct distribution profiles in different brain regions and different cell types. PrxI and VI are expressed in glial cells but not in neurons; while PrxII, III, IV and V are expressed in neurons. Various diseases or models show altered expression levels of these isozymes, such as by upregulation of PrxI, II and VI and downregulation of PrxIII. Thioredoxin (Trx)I mRNA is distributed widely in the rat brain. This distribution pattern may reflect the specific functions of these isozymes. Recently, the neuroprotective roles of Prx III and V against ibotenate-induced-excitotoxicity were reported by two independent groups. Adenovirus transduction of PrxIII eliminated protein nitration and prevented gliosis caused by direct infusion of ibotenate. Systemic administration of recombinant PrxV diminished brain lesions in animals treated with ibotenate. In this chapter, we review the causative mechanisms of oxidative stress in neurodegenerative diseases, as well as describe the basal and disease-induced changes in Prxs/Trxs/Trx reductases expression levels and neuroprotective roles of Trxs and Prxs as demonstrated in overexpression models.
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PMID:Peroxiredoxins in the central nervous system. 1808 3

Treatment with bone marrow stromal cells (BMSCs) ameliorates neurological functional deficits after stroke. Nerve growth factor (NGF) is a neurotrophic factor that supports the survival and growth of neural cells. Noggin, an antagonist of bone morphogenetic protein (BMP), promotes the differentiation of stem cells into neurons. In this study, we hypothesize that transfection of NGF and Noggin in BMSC treatment of stroke promotes BMSC neuronal differentiation and improves functional outcome after stroke. Adenovirus was used to trasfect NGF and Noggin and the transfection efficiency was measured by Western blot and immunostaining in vitro. The transfected BMSCs with NGF and/or Noggin were administered intravenously at 5 days after middle cerebral artery occlusion (MCAo) in rats. The neurological functional outcome and BMSC migration and differentiation in the ischemic brain were measured. The transplantation of BMSCs with NGF or Noggin elicited neurological functional improvement, promoted BMSCs present in the ischemic brain, and also up-regulated neuro-like cell differentiation as well as increased synaptophysin expression in the ischemic brain compared with nontreatment control animals (P< 0.05). Treatment of stroke with a combination of transfection of NGF and Noggin in BMSCs induced a synergistic effect on improved neurological functional outcome, BMSCs present in the ischemic brain, and synaptophysin expression in the ischemic brain compared with BMSCs transfected with an NGF- or Noggin-alone group (P < 0.05). These data demonstrate that increasing NGF or Noggin expression in BMSCs contributes to brain plasticity after stroke and that a synergistic effect is induced on the coexistence of NGF and Noggin in BMSCs treatment of stroke.
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PMID:Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. 2116 29