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)

The expression of interleukin-1 beta (IL-1 beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO). Whereas no IL-1 beta mRNA could be detected in non-operated and sham-operated rats, middle cerebral artery occlusion induced the expression of IL-1 beta mRNA within 15 min in the ischaemic brain regions prone to become necrotic after 1-2 days. The message appeared as spot-like signals, reached a peak after 3 h and then declined to undetectable levels within 4 days. Additionally, a pronounced but brief induction of IL-1 beta mRNA could be detected 1 h after MCAO in the meninges near the watershed zone. The results demonstrate that the inflammatory cytokine IL-1 beta is induced in a time-dependent way after brain ischaemia.
Brain Res Mol Brain Res 1994 Apr
PMID:Induction of interleukin-1 beta mRNA after focal cerebral ischaemia in the rat. 802 76

Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung, kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70 mRNA was normally expressed in a small amount in the cerebellum, lung, and kidney, but was not expressed in the heart or liver in a detectable amount. A very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70 mRNA was normally present in all the organs examined with a variety in the amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also increased in all the organs. However, the increase of HSC70 mRNA was remarkable in the heart. Transient cerebral ischemia caused subsequent hyperthermia. Treatment of gerbils with an artificial hyperthermia without cerebral ischemia increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level in the heart after cerebral ischemia was much higher than that in the case with hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially induced in the heart after transient forebrain ischemia that was not only due to the subsequent hyperthermia.
J Mol Cell Cardiol 1993 Oct
PMID:Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient brain ischemia. 826 47

Oxygen free radicals have been implicated as a causal factor in posttraumatic neuronal cell loss following cerebral ischemia and head injury. The conversion of salicylate to dihydroxybenzoic acid (DHBA) in vivo was employed to study the formation of hydroxyl radical (.OH) following central nervous system (CNS) injury. Bilateral carotid occlusion (BCO) in gerbils and concussive head trauma in mice were selected as models of brain injury. The lipid peroxidation inhibitor, tirilazad mesylate (U-74006F), was tested for its ability to attenuate hydroxyl radical formation in these models. In addition, U-74006F was studied as a scavenger of hydroxyl radical in an in vitro assay based on the Fenton reaction. For in vivo experimentation, hydroxyl radical formation was expressed as the ratio of DHBA to salicylate (DHBA/SAL) measured in brain. In the BCO model, hydroxyl radical formation increased in whole brain with 10 min of occlusion followed by 1 min of reperfusion. DHBA/SAL was also found to increase in the mouse head injury model at 1 h postinjury. In both models, U-74006F (1 or 10 mg/kg) blocked the increase in DHBA/SAL following injury. In vitro, reaction of U-74006F with hydroxyl radical gave a product with a mol wt that was 16 greater than U-74006F, indicative of hydroxyl radical scavenging. We speculate that U-74006F may function by blocking oxyradical-dependent cell damage, and thereby maintaining free iron (which catalyzes hydroxyl radical formation) concentrations at normal levels.
Mol Chem Neuropathol 1993 Oct
PMID:The use of salicylate hydroxylation to detect hydroxyl radical generation in ischemic and traumatic brain injury. Reversal by tirilazad mesylate (U-74006F). 829 19

This article briefly reviews the importance and relevance of membrane lipid degradation to the pathogenesis of ischemic brain damage ranging from the liberation and accumulation of free fatty acids (FFA) to their consequences on the biophysical characteristics of membrane lipids. The rapid accumulation of brain FFA during cerebral ischemia is a hallmark of the evolution and pathogenesis of ischemic brain damage: It signals the degradation of membrane lipids; it generates the precursors to the metabolically and physiologically potent eicosanoids; and it promotes the generation of lipid oxidizing free radicals, which could propagate the destruction of membrane lipids. The impact of ischemia-induced changes in cerebral membrane lipid composition on membrane function is difficult to assess in vivo. Some estimate of the impact of the changes, however, can be obtained by evaluating the changes induced in the surface pressure-area diagrams (SPAD) of membrane lipid monolayers at the air-water interface. Lipid monolayers are used as model membranes to study the effects of lipid composition on the biophysical behavior of membrane lipids and their interaction. Regional brain lipids were quantitated at different times during ischemia, and their impact on their surface pressure area diagrams was assessed and their potential impact on membrane function discussed.
Mol Chem Neuropathol
PMID:Membrane lipid degradation during ischemia and impact on the monolayer surface pressure area diagram (SPAD). 836 5

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome c oxidase subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively decreased in the hippocampal CA1 neurons of gerbils from 1 to 3 h of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells, and significantly decreased at 7 days. These results suggest that disturbance of mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in the neuronal cell death.
Brain Res Mol Brain Res 1993 Jul
PMID:Disturbance of a mitochondrial DNA expression in gerbil hippocampus after transient forebrain ischemia. 839 30

The phenylalkylamine emopamil prevents brain damage due to experimental cerebral ischemia. Stereoselective, high affinity, binding sites for (-)-[3H]emopamil in guinea pig brain cortex and liver membranes have been proposed to mediate its antiischemic effect. Using [N-methyl-3H]LU49888 as a photoaffinity probe we now provide evidence that the cation-sensitive emopamil binding site is localized on a 22-kDa polypeptide in guinea pig liver, kidney, lung, and adrenal gland. This 22-kDa polypeptide binds other antiischemic drugs with high affinity and is a nonglycosylated integral membrane protein of the endoplasmic reticulum. It can be solubilized with digitonin without changes in its drug-binding properties. The solubilized binding activity has a sedimentation coefficient of 12.0 +/- 0.4 S and an apparent Stokes radius of 6.0 +/- 0.1 nm. From these data it is concluded that the 22-kDa polypeptide is associated in a larger oligomeric complex with a molecular mass of at least 84 kDa. [N-methyl-3H]LU49888 also specifically labels a second 27-kDa polypeptide in the endoplasmic reticulum, which can be distinguished from the 22-kDa polypeptide by its pharmacological and hydrodynamic properties. The photolabeled 22-kDa polypeptide was partially purified under denaturating conditions. This will allow the further structural analysis of this putative target for antiischemic drugs.
Mol Pharmacol 1993 Feb
PMID:Biochemical characterization of a 22-kDa high affinity antiischemic drug-binding polypeptide in the endoplasmic reticulum of guinea pig liver: potential common target for antiischemic drug action. 842 20

Regionally selective delayed neuronal degeneration is a characteristic sequel of cerebral ischemia. Recent evidence indicates that changes in brain polyamine metabolism may be critical for nerve cell survival after ischemia. Within hours after ischemia, intracellular putrescine levels are greatly increased and remain elevated for days, whereas only minor changes are noted in the levels of the polyamines spermine and spermidine. In contrast, the extracellular levels of all polyamines are low after ischemia. Injections of polyamines following ischemia, however, can protect neurons in the gerbil brain from delayed cell death, with spermine being the most potent of the polyamines. In the present study, therefore, we sought to determine if increased polyamine uptake occurs in the brain after ischemia. In the hippocampal slice preparation, temperature-dependent uptake was unique for spermine, but not for spermidine or putrescine. Uptake of [14C]spermine was transiently increased after ischemia, peaking at 150% of control by 12-13 h and subsiding by 24 h. Intravenous injections of [3H]spermidine resulted in a postischemic accumulation of this polyamine throughout the forebrain parenchyma. We conclude that: 1. Active cellular uptake of spermine is transiently increased early after ischemia; 2. A nonspecific accumulation of exogenous polyamines occurs early after ischemia probably owing to a compromised blood-brain barrier, and 3. The findings indicate that exogenous polyamines can exert their effect directly in the brain after ischemia.
Mol Chem Neuropathol
PMID:Accumulation of exogenous polyamines in gerbil brain after ischemia. 846 93

The transport of glutathione (GSH) or glutathione isopropyl ester (GSH isopropyl ester) to the cerebrospinal fluid (CSF) in rats was estimated by levels of GSH or GSH isopropyl ester and their metabolites in CSF 30 min after the intravenous administration of GSH or GSH isopropyl ester (300 mg/kg). Although the CSF uptake of GSH isopropyl ester was almost equal to that of GSH as evidenced by about a two-fold increase in the amount of non-protein sulfhydryl groups in CSF, the sum of GSH isopropyl ester and GSH concentrations in the CSF after GSH isopropyl ester treatment was increased by 32% compared with saline-treated controls. On the other hand, treatment with GSH had no significant increase in GSH levels in CSF but increased its metabolite levels, such as cysteinyl-glycine and cysteine. GSH isopropyl ester was less metabolized than GSH. GSH isopropyl ester had low affinity to purified gamma-glutamyl transpeptidase, a key enzyme for metabolism of GSH in the choroid plexus, supporting the finding that GSH isopropyl ester is more stable than GSH in CSF. These results are compatible with our previous report (Yamamoto et al. (1993) showing that the protective action of GSH isopropyl ester against cerebral ischemia was greater than that of GSH in rats. GSH isopropyl ester may be a useful agent which protects the brain from the damage associated with oxygen-related toxicities by increasing GSH levels in the CSF.
Res Commun Mol Pathol Pharmacol 1995 Jun
PMID:Transport and metabolism of glutathione isopropyl ester in cerebrospinal fluid. 856 90

The excitatory amino acids (EAA) are involved in the pathogenesis of the cerebral ischemia. Moreover, several investigators have demonstrated that a considerable amount of dopamine (DA) is released in the striatum after ischemia reperfusion/insult (IRI). Recently, studies have demonstrated in vitro, that D-2 agonist, at the level of striatum and retina, may represent a powerful signal to inhibit release of excitatory amino acids implicated in cerebral ischemia. Therefore we have been incited to test, in vivo, the action of a D-2 agonist, piribedil, on gerbil brain after IRI. We have used the Stroke Index (SI); then to precise the mechanism of action, we have determined the levels of dopamine, EAA, and hydroxyl-free radicals (OH), in striatum, hippocampus, and hemisphere. Piribedil, administered at dose of 10 mg/kg, per os, 60 min before induction of transient cerebral ischemia in gerbils, presents a neuroprotective effect, as measured by SI and significantly reverses the increase of DA, EAA, and OH induced by IRI. The mechanism of action of piribedil could be related to its D-2 agonist property.
Mol Chem Neuropathol 1995 Sep
PMID:Effect of piribedil, a D-2 dopaminergic agonist, on dopamine, amino acids, and free radicals in gerbil brain after cerebral ischemia. 858 23

We examined the effect of reversible ischemia on the transcription of prostaglandin endoperoxide synthase (PGHS-1) and c-fos mRNA in rat cerebral cortex. The level of PGHS-1 mRNA climaxed after 30 min of ischemia whereas transcription of c-fos mRNA peaked after 60 min of postischemic reperfusion. We conclude that cerebral ischemia causes early transcription of PGHS-1, without modulation by the c-fos gene or its translated product.
Brain Res Mol Brain Res 1996 Jan
PMID:Induction of PGH synthase and c-fos mRNA during early reperfusion of ischemic rat brain. 871 74


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