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)

Subarachnoid hemorrhage (SAH) was produced in Sprague Dawley rats by injection of 0.30 mL of autologous arterial blood into the cisterna magna. Tissue lipid peroxide, quantified as thiobarbituric acid reactive material (TBAR), and Na+,K(+)-ATPase activity were assayed in three different rat brain areas (cerebral cortex, hippocampus, and brain stem) of sham-operated rats and in four hemorrhagic rat groups at 30 min, 1 h, 6 h, and 2 d after SAH. Na+,K(+)-ATPase activity decreased in the cerebral cortex at 30 min, 1 h, and 6 h and in the brain stem at 1 h after SAH induction, whereas enzymatic activity was unchanged in the hippocampus. There was no evident difference in lipid peroxide content between sham-operated animals and hemorrhagic animals. These results indicate that little modifications in lipid peroxidative process (as expressed in TBAR) are not responsible for changes in the ATPase activity.
Mol Chem Neuropathol 1989 Oct
PMID:Experimental subarachnoid hemorrhage. Lipid peroxidation and Na+,K(+)-ATPase in different rat brain areas. 256 16

1. We investigated the function of monoaminergic neurons in the lower brain stem following subarachnoid hemorrhage (SAH) induced in rats, by measuring monoamine metabolites, using in vivo microdialysis techniques. 2. A dialysis probe was implanted in the nucleus tractus solitarius (NTS) and the perfusates were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection (ECD). 3. The main monoamine metabolites measured in the NTS extracellular space were 3,4-dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). 4. Monoamine metabolites in the rat NTS were nonspecifically increased, at least in the acute phase after cisternal injection of blood or saline. 5. The disappearance rates of the 5-HIAA decline and the early phase of DOPAC decline after pargyline administration (75 mg/kg, i.p.) were most rapid at 2 days after the induction of SAH, then recovered gradually. 6. These results suggest that functions of noradrenergic and serotonergic neurons in the NTS may be disturbed predominantly in the case of induced vasospasm in rats.
Cell Mol Neurobiol 1993 Dec
PMID:Changes in monoaminergic neuronal function in the lower brain stem following subarachnoid hemorrhage induced in rats. 751 58

The production of oxygen-free radicals and their subsequent peroxidative action on membrane unsaturated fatty acids could be enhanced after subarachnoid hemorrhage (SAH). We have studied the effects of the in vivo pharmacological treatment with a lazaroid (U78517F) after experimental SAH, on lipid peroxidative patterns in cortical synaptosomal preparations. U78517F is a lipid-soluble antioxidant with a potent action to inhibit iron-dependent lipid peroxidation. Experimental SAH was induced in anesthetized rats by slow injection of 0.3 mL of autologous arterial blood into cisterna magna. The hemorrhagic animals were treated with 5 mg/kg iv of U78517F immediately after surgical operation. The animals were sacrificed 1 d after the hemorrhage and the thiobarbituric acid reactive material (TBAR) was assayed in basal conditions and after 1, 3, 5, 10, and 20 min of incubation at 37 degrees C with a pro-oxidant mixture on three different rat groups: sham-operated (0.3 mL of mock cerebrospinal fluid (CSF) into cisterna magna), hemorrhagic (0.3 mL of autologous arterial blood into cisterna magna), and hemorrhagic-treated. The hemorrhagic event did not influence the membrane lipoperoxidation levels in basal conditions, whereas peroxidative stimulation in vitro caused significant increases in hemorrhagic animals compared to the sham-operated, and in hemorrhagic-treated animals, the synaptosomal TBARs were similar to controls. The pharmacological treatment showed its effectiveness only following incubations with pro-oxidants; therefore, U78517F seems to be protective for membranes in case of severe lipid peroxidative stress.
Mol Chem Neuropathol
PMID:Synaptosomal iron-dependent lipid peroxidation inhibition after subarachnoid hemorrhage by lazaroid in vivo treatment. 913 26

Carbon monoxide (CO) is an endogenously generated gas that may play an important physiological role in the circulation. CO is generated by vascular cells as a byproduct of heme catabolism, in which heme oxygenase (HO) catalyzes the degradation of heme to biliverdin, iron and CO. Two distinct isoforms of HO have been identified in vascular tissue. The HO-2 isoform is constitutively expressed and likely mediates the release of CO under normal physiologic conditions. In contrast, the HO-1 isoform is strongly induced in vascular cells by various stress-associated agents and markedly increases CO synthesis during pathological conditions. The release of CO by vascular cells exerts both paracrine and autocrine effects on vascular smooth muscle cells (SMC) and circulating blood cells. CO regulates blood flow and blood fluidity by inhibiting vasomotor tone, SMC proliferation, and platelet aggregation. These vascular effects of CO are mediated via the activation of soluble guanylate cyclase and the consequent rise in intracellular guanosine 3',5'-cyclic monophosphate levels in target tissues. CO may also play a role in various cardiovascular disorders, including endotoxin shock, ischemia-reperfusion, hypertension, and subarachnoid hemorrhage. This review will focus on the recent progress made in understanding the regulation and function of CO in the vasculature.
Int J Mol Med 1998 Sep
PMID:Carbon monoxide and vascular cell function (review). 985 96

The initial aim of this study was to determine if the HSP70 (the main inducible heat shock protein), HO-1 (heme oxygenase-1, HSP32) and HSP47 (a collagen chaperone) stress proteins were induced in the same focal regions of rat brain following experimental subarachnoid hemorrhage (SAH). The next objective was to determine whether anti-oxidants prevented the stress gene expression in the focal regions. Lysed blood (150 microliter) was injected into the subarachnoid space of adult, female Sprague-Dawley rats via the cisterna magna. Animals were sacrificed 24 h later. Immunocytochemistry showed focal regions of stress gene induction in most animals (13/21), HSP70 and HO-1 proteins being expressed in neurons, microglia and astrocytes and HSP47 being expressed in microglia. Co-induction of the same three stress proteins was observed in focal areas in the striatum and cerebellum as well. In the 13 animals with focal regions of stress gene induction there were 8.1+/-1.8 foci in cortex, 5.5+/-0.9 foci in striatum, and 11.7+/-7.3 foci in cerebellum in the brain of each animal. The focal regions of stress gene induction varied in size from 200 micrometer to 7 mm in diameter. Systemic administration of the tirilazad-like anti-oxidants U101033E (n=8) and U74389G (n=7) completely blocked stress protein induction in focal brain regions normally produced by cisternal injections of lysed blood. There were fewer drug treated animals (0/15) with focal areas of stress gene induction compared to non-drug (13/21) treated animals following the cisternal lysed blood injections (p<0.01 using Fisher's probability test). This study shows that anti-oxidants prevent focal regions of injury as assessed by heat shock protein expression in a rat model of SAH.
Brain Res Mol Brain Res 1999 Feb 19
PMID:Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood. 1003 11

1. Approximately one-third of the morbidity and mortality due to aneurysmal subarachnoid hemorrhage (SAH) is caused by delayed ischemic neurological deficit (DIND) due to cerebral vasospasm. 2. Compared to prolonged arterial constriction in other parts of the body, cerebral vasospasm is characterized by its long duration and refractoriness to vasodilators such as calcium antagonists. 3. Whereas oxyhemoglobin (oxyHb) liberated into the CSF from the subarachnoid clot has been deemed the causative agent of vasoconstriction, the biochemical mechanisms whereby oxyHb elicits prolonged constriction of the cerebral arteries has remained elusive. Here, we suggest that oxyHb triggers the generation of reactive oxygen intermediates (ROI) within the CSF. 4. Multiple lines of evidence indicate that the occurrence of vasospasm, namely, prolonged smooth muscle contraction, is due to the following intracellular events. 5. First, hydroxyl radicals (OH*), the most reactive species of ROI, are generated within the cerebral arterial wall via the Fenton and Haber-Weiss reactions catalyzed by oxyHb. Second, subsequent peroxidative membrane damage in the arterial smooth muscle cell enhances the metabolism of phosphatidylcholine and phosphatidylethanolamine, leading to a rise in the intracellular level of diacylglycerol, an endogenous activator of protein kinase C. 6. The prolonged arterial contraction that occurs during vasospasm is attributable primarily to the activation of protein kinase C, not to the Ca2+/calmodulin system. In this article, literature relevant to the above thesis is reviewed, and the rationale for the antioxidant therapy against cerebral vasospasm is discussed.
Cell Mol Neurobiol 1999 Feb
PMID:Antioxidant therapy against cerebral vasospasm following aneurysmal subarachnoid hemorrhage. 1007 63

Endothelin receptor antagonists have been proposed for the treatment of a variety of disorders in which the endothelins may act as pathogenic mediators, such as congestive heart failure, systemic and pulmonary hypertension, and cerebral vasospasm. Bosentan (Ro 47-0203) is a nonpeptide competitive antagonist, which can be a good tool for studying the endothelin system because it may be administered either acutely or chronically. It is specific for the endothelin system and blocks the actions of endothelin at both mammalian receptors (A and B). In experimental models of heart failure bosentan acts as a vasodilator and neurohormonal blocker that improves overall left ventricular performance and reduces renal dysfunction. Furthermore, in chronic studies, bosentan attenuates cardiac remodeling and significantly improves survival. In patients with chronic heart failure bosentan produces pulmonary and systemic vasodilation and may enhance conventional treatment with angiotensin-converting enzyme inhibitors. Long-term studies are being conducted to characterize the full therapeutic potential of bosentan in chronic heart failure. In experimental models bosentan reverses established pulmonary hypertension. Preclinical efficacy has also been demonstrated in essential hypertension, where bosentan can reduce blood pressure and end-organ damage. Clinical trials in hypertensive patients indicate that bosentan reduces blood pressure without heart rate increase or neurohumoral stimulation. Finally, bosentan is being considered for the treatment of cerebral vasospasm following subarachnoid hemorrhage. Bosentan reverses experimentally induced vasospasm of the basilar artery, and preliminary trials indicate that it can increase cerebral blood flow after aneurysmal subarachnoid hemorrhage.
J Mol Med (Berl) 1999 Apr
PMID:Endothelin antagonism with bosentan: a review of potential applications. 1035 41

The use of gene transfer systems to study cell function makes it apparent that overexpression of a transgene can restore or improve the function of a protein and positively influence cell function in a predetermined manner for purposes of counterbalancing cellular pathophysiology. The ability of some gene transfer vehicles to produce transgene product within hours of delivery positions gene transfer as a unique pharmaceutical administration system that can quickly affect production of biologic response modifiers in a highly compartmentalized fashion. This approach can be expected to overcome many of the adverse effects and high costs of systemic delivery of recombinant pharmaceuticals. This review highlights recent advances toward development of gene therapies for acute illnesses with particular emphasis on preclinical models of disease. In this context, a growing body of data suggests that gene therapies for polygenic and non-genetic diseases such as asthma, cardiogenic and non-cardiogenic pulmonary edema, stroke, subarachnoid hemorrhage, seizures, acute myocardial infarction, endovascular thrombosis, and infections may someday be options for the treatment of patients.
Mol Ther 2001 Dec
PMID:Gene therapy for acute diseases. 1173 35

Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may be reduced in patients with normal pressure hydrocephalus (NPH) after subarachnoid haemorrhage (SAH). However, little is known about brain circulation in asymptomatic patients with ventriculomegaly after SAH. This study investigated CBF and CVR in symptomatic and asymptomatic patients with ventriculomegaly to clarify the mechanism of NPH. CBF and CVR were investigated in 48 patients with ventriculomegaly after SAH due to ruptured aneurysm. Mean CBF of the whole brain was measured by first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after administration of 500 mg acetazolamide. Thirty patients with NPH who responded to shunting had significantly ( P<0.01) reduced mean CBF and CVR compared with normal controls. Fourteen asymptomatic patients with ventriculomegaly showed significant ( P<0.01) reduction in CVR but no difference in mean CBF. Four symptomatic patients who did not respond to shunting showed significantly ( P<0.01) reduced mean CBF but had preserved CVR. Postoperative mean CBF and CVR increased significantly ( P<0.01) in 21 patients who responded to shunting, but showed no significant change in four symptomatic patients who did not respond to shunting. Reduction of CBF superimposed on pre-existing impairment of CVR may be an essential step in the mechanism responsible for the manifestation of symptoms of NPH.
Eur J Nucl Med Mol Imaging 2003 Jan
PMID:Cerebral haemodynamics in patients with hydrocephalus after subarachnoid haemorrhage due to ruptured aneurysm. 1248 19

Cigarette smoking is known to be one of the risk factors of subarachnoid hemorrhage (SAH), yet the precise mechanism remains to be proved. Based on the hypothesis that smoke components might enhance protease activity in the arterial wall, we examined the proteinase activities of plasma from smoke-extract-injected rats. Rats were injected intraperitoneally with smoke extract and the protease activity in the plasma was examined by zymography in the presence or the absence of proteinase inhibitors. Metalloproteinase activity was measured using a synthetic substrate. Proteolytic activities of 80- and 100-kDa against gelatin and collagen type I-V were induced 6 h after the injection. Inhibition of the activity by a metalloproteinase inhibitor but not by serine, cysteine or aspartic protease inhibitors suggested that the proteinases can be attributed to metalloproteinases. Cleavage activity in plasma toward a synthetic metalloproteinase substrate also increased within 24 h after the injection of the smoke extract. The results indicate that the induction of plasma metalloproteinase activity by smoke extract might account for the causal role of smoking in the development of SAH.
Int J Mol Med 2004 Oct
PMID:Increase in metalloproteinase activity in the plasma of smoke-extract-injected rats. 1537 98


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