Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies indicate that apoptosis in endothelial cells of major cerebral arteries contributes to cerebral vasospasm after subarachnoid hemorrhage (SAH). This study examined the pathologic roles of tumor suppressor p-53 in cerebral vasospasm using an established dog double-hemorrhage model. Twenty mongrel dogs were divided into four groups: (1) control, (2) SAH, (3) SAH+DMSO (vehicle), and (4) SAH+pifithrin-alpha (PFT) (p53 inhibitor). The p53 inhibitor (200 nmol/L) was injected into the cisterna magna daily from Day 0 through Day 3. Angiogram was performed on Day 0 and Day 7. Western blot, cell proliferation assay, histology, and TUNEL staining were conducted on the basilar arteries collected on Day 7 after SAH. The arterial diameter on Day 7 was 42%+/-4%, 40%+/-5%, and 59%+/-4% for SAH, SAH+DMSO, and SAH+PFT, respectively. In addition, positive staining of TUNEL and increased protein expression of p53, Bax, and PCNA in the basilar artery were observed on Day 7. PFT suppressed apoptosis in endothelial cells and proliferation in smooth muscle cells, and attenuated angiographic vasospasm. In conclusion, p53 may be a key factor in endothelial apoptosis and smooth muscle proliferation after SAH. Inhibition of p53 may potentially reduce or even prevent cerebral vasospasm.
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PMID:Role of p53 and apoptosis in cerebral vasospasm after experimental subarachnoid hemorrhage. 1572 95

This study was designed to explore the effects of Tetramethylpyrazine on cerebral vasospasm and early brain injury and its underlying mechanisms after experimental SAH in rats. Male Sprague-Dawley rats (n=164) were allocated randomly to SAH+TMP, SAH+vehicle (sodium chloride), or sham-operated group. The SAH model was induced through perforating internal carotid artery. TMP (30 mg/kg) or the vehicle was injected via vena caudalis 60 min before the perforation. Mortality, neurological scores, water content of brain and cerebral vasospasm were recorded at 24 h after SAH. Apoptosis of cerebral cortex was determined by TUNEL staining; caspase-3, bax and bcl-2 by Western blotting; P53 expression by immunohistochemical staining. TMP administrated in advance improved neurological scores, ameliorated cerebral edema and cerebral vasospasm. TUNEL-positive cells were reduced significantly in TMP-treated group. P53 was not found significantly different between TMP-treated and vehicle-treated group, while P53 positive cells were markedly higher in SAH group than that in sham-operated group. Cleaved caspase-3 protein was decreased significantly in TMP-treated group, while bax, bcl-2 protein expression did not differ statistically among the three groups. In conclusion, TMP ameliorated cerebral vasospasm and early brain injury after experimental SAH in rats. The underlying mechanisms may be partly related to inhibition of caspase-3 dependent proapoptosis pathway.
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PMID:Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following subarachnoid hemorrhage in rats. 1855 17

Stroke is the second leading cause of death worldwide and the number one cause of adult disability in the United States and Europe. A subtype of stroke, subarachnoid hemorrhage (SAH), accounts for 7% of all strokes each year and claims one of the highest mortalities and morbidities. Many therapeutic interventions have been used to treat brain injury following SAH but none have reached the level of effectiveness needed to clinically reduce mortality. Ginsenoside Rb1 (GRb1), a major component of the Chinese traditional medicine Panax Ginseng, has been shown to reduce ischemic brain injury and myocardial injury via anti-apoptotic pathways. In the present study, we investigated the use of GRb1 on SAH induced brain injury in rats. Four groups were used: sham, vehicle (SAH), low dose treatment (SAH+ 5mg/kg GRb1), and high dose treatment (SAH+ 20mg/kg GRb1). Post assessment included wall thickness and mean cross-section area of basilar artery were measured for evaluating cerebral vasospasm, Evans blue extravasations to assess blood brain barrier (BBB) permeability, immunohistochemistry and Western Blot analysis looking for specific pro-apoptotic markers, and tunnel staining for cell death assessment. In addition, mortality, neurological function and brain edema were investigated. The results showed that high dose GRb1 treatment significantly enlarged mean cross-sectional area and decreased wall thickness of basilar artery, reduced neurological deficits, brain edema, BBB disruption, and TUNEL positive cell expression. Same time, we found that the proteins expression of P53, Bax and Caspase-3 were significantly reduced, whereas the expression of bcl-2 was up-regulated in Rb1 treatment. The results of this study suggest that GRb1 could relieve cerebral vasospasm and potentially provide neuroprotection in SAH victims. The underlying mechanisms may be partly related to inhibition of P53 and Bax dependent proapoptosis pathway. More studies will be needed to confirm these results and determine its potential as a long term agent.
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PMID:Ginsenoside Rbeta1 reduces neurologic damage, is anti-apoptotic, and down-regulates p53 and BAX in subarachnoid hemorrhage. 2035 83

The effect of 2,2'-dipyridyl (DP) on cerebral vasospasm was investigated in a double-injection rabbit model of subarachnoid haemorrhage (SAH). Thirty-six animals were divided between four groups: control (sham-operated), SAH (model alone), SAH + DP (the SAH model in which DP dissolved in dimethyl sulphoxide [DMSO] was injected once daily for 5 days into the cisterna magna), and SAH + DMSO (the SAH model in which DMSO [vehicle] was injected daily for 5 days). There were significant differences in the basilar artery luminal area, wall thickness, neurological deficit score and vasospasm index between the SAH + DP and SAH groups. There was a significant negative correlation between arterial luminal area and arterial wall thickness, and also between the neurological deficit score and vasospasm index. Cells that were positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) and p53 expression were significantly increased in the SAH + DMSO and SAH groups, but not in the SAH + DP group, versus controls. Thus, DP may attenuate cerebral vasospasm after SAH by suppressing p53-induced apoptosis in the cerebral vessels.
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PMID:Ferrous chelator 2,2'-dipyridyl attenuates cerebral vasospasm after experimental subarachnoid haemorrhage in rabbits. 2051 71

Subarachnoid hemorrhage (SAH) is a devastating stroke subtype accounting for approximately 3 to 7% of cases each year. Despite its rarity among the various stroke types, SAH is still responsible for approximately 25% of all stroke fatalities. Although various preventative and therapeutic interventions have been explored for potential neuroprotection after SAH, a considerable percentage of patients still experience serious neurologic and/or cognitive impairments as a result of the primary hemorrhage and/or secondary brain damage that occurs. Z-ligustilide (LIG), the primary lipophilic component of the Chinese traditional medicine radix Angelica sinensis, has been shown to reduce ischemic brain injury via antiapoptotic pathways. Accordingly, in our study, we investigated the neuroprotective potential of LIG after experimental SAH in rats. Rats with SAH that was induced using the established double hemorrhage model were studied with and without LIG treatment. Mortality, neurobehavioral evaluation, brain water content, blood-brain barrier (BBB) permeability, and vasospasm assessment of the basilar artery were measured on days 3 and 7 after injury. Additional testing was done to evaluate for apoptosis using TdT-mediated dUTP-biotin nick end labeling staining as well as immunohistochemistry and Western blotting to identify key proapoptotic/survival proteins, i.e., p53, Bax, Bcl-2, and cleaved caspase-3. The results showed that LIG treatment reduced mortality, neurobehavioral deficits, brain edema, BBB permeability, and cerebral vasospasm. In addition, treatment reduced the number of apoptotic cells in the surrounding brain injury site, which accompanied a marked down-regulation of proapoptotic proteins, p53, and cleaved caspase-3. Our data suggest that LIG may be an effective therapeutic modality for SAH victims by altering apoptotic mechanisms.
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PMID:Treatment with Z-ligustilide, a component of Angelica sinensis, reduces brain injury after a subarachnoid hemorrhage in rats. 2139 13