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)

Recent evidence suggests that insulin-like growth factor-I (IGF-I) acts as a neurotrophic factor in the injured CNS. The role of the related peptide IGF-II is unclear. Therefore, we compared the induction of IGF-II in the developing rat brain following mild or severe hypoxic-ischemic (HI) injuries. Ligation of the right carotid artery of 21 day old rats followed by either 15 or 60 min exposure to 8% oxygen led to mild or severe unilateral damage respectively. Brains were collected at 1 day, 3, 5, 7 and 10 days, post-hypoxia. In situ hybridization showed that the 15 min injury (which produced selective neuronal loss) produced no change in basal IGF-II gene expression. However, the 60 min injury, which resulted in cortical infarction and severe neuronal loss in other regions, led to the induction of IGF-II mRNA mainly in the infarcted cortex, from 5-7 days post-hypoxia. Immunohistochemical analysis of brains collected 10 days after the 60 min injury showed that IGF-II immunoreactivity (IR) was also increased, predominantly in damaged regions, but also in the contralateral hippocampus. IGF-II IR was associated with non-neuronal cells that appeared to be microglial-like cells and astrocytes. Together these data suggest that IGF-II may modulate the response of glial cells during recovery from cerebral infarction.
Brain Res Mol Brain Res 1995 Mar
PMID:Insulin-like growth factor II is induced during wound repair following hypoxic-ischemic injury in the developing rat brain. 777 4

We examined activation of the transcription factor, nuclear factor-kappaB (NF-kappaB), which participates in the upregulation of endothelial cell adhesion proteins, during reperfusion after temporary middle cerebral artery occlusion (TMCAO). We hypothesized that N-acetylcysteine (NAC), an antioxidant which inhibits NF-kappaB activation, would alter events in brain reperfusion injury. We used a rat model of TMCAO. The left sides of the brains were rendered ischemic for 2 h, and then the area was allowed to reperfuse. The animals were treated with NAC (150 mg/kg) or saline placebo, sacrificed, and activated NF-kappaB was assessed in both the left and right hemispheres, all at varying intervals. Cerebral infarction volume was also measured in each of the hemispheres collected from a separate group of animals. Activated NF-kappaB, consisting of p65 and p50 Rel proteins, was significantly increased 15 min after reperfusion in the affected hemisphere. The activation at 15 min was completely abolished with NAC treatment. NAC treatment 1 h prior to the end of occlusion and at 24 h reduced the percentage infarction volume of the affected hemispheres from 35.5+/-2.8% (S.E.) to 18. 1+/-2.1% (p<0.01). NAC treatment at 1 h after the occlusion (after the NF-kappaB peak) and again at 24 h also significantly reduced the percentage infarction volume from 34.8+/-3.8% to 24.6+/-3.8% (p<0. 05). Thus, while NAC inhibited activation of NF-kappaB at 15 min after reperfusion, the drug acted to reduce cerebral infarction by additional, undefined mechanisms. These results bring into question the various roles of NF-kappaB in cerebral infarction followed by reperfusion.
Brain Res Mol Brain Res 1998 May
PMID:Nuclear factor-kappa B activation during cerebral reperfusion: effect of attenuation with N-acetylcysteine treatment. 960 21

1. We review the biochemical and molecular changes in brain with developing cerebral infarction, based on recent findings in experimental focal cerebral ischemia. 2. Occlusion of a cerebral artery produces focal ischemia with a gradual decline of blood flow, differentiating a severely ischemic core where infarct develops rapidly and an area peripheral to the core where the blood flow reduction is moderate (called penumbra). Neuronal injury in the penumbra is essentially reversible but only for several hours. The penumbra area tolerates a longer duration of ischemia than the core and may be salvageable by pharmacological agents such as glutamate antagonists or prompt reperfusion. 3. Upon reperfusion, brain cells alter their genomic properties so that protein synthesis becomes restricted to a small number of proteins such as stress proteins. Induction of the stress response is considered to be a rescue program to help to mitigate neuronal injury and to endow the cells with resistance to subsequent ischemic stress. The challenge now is to determine how the neuroprotection conferred by prior sublethal ischemia is achieved so that rational strategies can be developed to detect and manipulate gene expression in brain cells vulnerable to ischemia. 4. Expansion of infarction may be caused by an apoptotic mechanism. Investigation of apoptosis may also help in designing novel molecular strategies to prevent ischemic cell death. 5. Ischemia/reperfusion injury is accompanied by inflammatory reactions induced by neutrophils and monocytes/macrophages infiltrated and accumulated in ischemic areas. When the role of the inflammatory/immune systems in ischemic brain injury is revealed, new therapeutic targets and agents will emerge to complement and synergize with pharmacological intervention directed against glutamate and Ca2+ neurotoxicity.
Cell Mol Neurobiol 1999 Feb
PMID:Biochemical and molecular characteristics of the brain with developing cerebral infarction. 1007 69

Cytokines in the central nervous system (CNS) may play an important role in functioning as intercellular signals that orchestrate the response to injury. Whether this is a cause or result of the brain disease process is uncertain. We investigated IFN-gamma, IL-2, IL-4, IL-6, and IgE in the sera of 38 patients with cerebral infarction during the acute stage and 10 normal controls using an originally devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA). We found that serum levels of IL-2 derived from T helper 1 (Th1) cells were slightly reduced in patients with cerebral infarction, whereas serum levels of IL-4 and IL-6 derived from Th2 cells were elevated significantly. IL-4 induces synthesis of IgE in human B cells. Endogenous IL-6 plays an obligatory role in IL-4-dependent human IgE synthesis. We observed that serum IgE levels were elevated significantly in patients with cerebral infarction. However, serum IFN-gamma levels were not elevated significantly in cerebral infarction patients. These findings suggest that elevated IL-4, IL-6, and IgE levels in the human serum may be an important factor in cerebral infarction during the acute stage. Decrease of IL-2 levels in the serum of patients with cerebral infarction may be a regulatory mechanism.
J Mol Neurosci 2000 Jun
PMID:Reduced IL-2 but elevated IL-4, IL-6, and IgE serum levels in patients with cerebral infarction during the acute stage. 1098 95

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (chi2 = 0.128, p = 0.720). The frequencies of the genotypes of the ACE gene were II: 39.6%, ID: 45.3%, and DD: 15.1% in patients, and II: 37.1%, ID: 47.6%, and DD: 15.3% in controls (chi2 = 0.127, p = 0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.
J Mol Neurosci 2001 Dec
PMID:Polymorphism of the angiotensin-converting enzyme gene in patients with cerebral infarction in Koreans. 1185 23

Using a bone-marrow transplantation chimera-model in mice, we have shown that after a cerebral infarction, bone marrow-derived cells differentiate into cerebral endothelial cells and NeuN-expressing cells
Trends Mol Med 2002 Sep
PMID:Blood into brain after stroke. 1222 18

Interleukin-1 (IL-1) has pleiotropic actions in the central nervous system. During the last decade, a growing corpus of evidence has indicated an important role of this cytokine in the development of brain damage following cerebral ischemia. The expression of IL-1 in the brain is dramatically increased during the early and chronic stage of infarction. The IL-1 gene cluster on chromosome 2q14 contains three related genes (IL1alpha, IL1beta, and IL1 receptor antagonist) located within a 430-kb region. T and C alleles exist for the IL-1alpha-889 regulatory region and the TT genotype has been reported to increase the production of the protein in lipopolysaccharide (LPS)-stimulated mononuclear cells from IL-1alpha-889 TT carriers. We examined whether the IL-1alpha polymorphism affects the probability of cerebral infarction (CI). We genotyped 360 CI patients and 519 healthy controls for the same polymorphism. A significant increase was found for the IL-1alpha T allele in CI patients compared with controls (chi2=5.026, P=0.025). We conclude that the IL-1alpha-889 polymorphism is a major risk factor for CI in Koreans.
Brain Res Mol Brain Res 2003 Jul 04
PMID:Association of interleukin-1 alpha gene polymorphism with cerebral infarction. 1282 54

The homozygous deletion allele of the angiotensin-converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the epsilon4 allele of the apolipoprotein E gene (apoE/epsilon4) are reported to be associated with ischemic heart disease. Cerebral infarction (CI) is another atherosclerotic disease, and the effects of these polymorphisms on CI have been confusing. The frequency of the DD genotype of the ACE gene, but not the TT genotype of the AGN gene and the epsilon4 allele of ApoE, was significantly higher in subjects with than those without CI in Japan. In this study, we investigated whether ACE/DD, AGN/TT, and apoE/epsilon4 genotypes are associated with CI and whether genetic risk is enhanced by the effect of one upon another. We ascertained these genotypes in patients with CI (n = 365), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. Frequency of the AGN/TT genotype was higher in patients with CI than in controls (chi2 = 12.287, p < 0.05). The frequency of t allele was 0.88 in patients and 0.82 in controls (chi2 = 11.041, p < 0.05; odds ratio, 1.7). Furthermore, the AGN/TT genotype increased the relative risk for CI in subjects with the ACE/DD genotype (chi2 = 7.8, p < 0.05; odds ratio, 1.9). There was no significant association between apoE/epsilon4 and CI. These results suggest that AGN/TT predicts CI and ACE/DD enhances the risk for CI associated with AGN/TT in a Korean population.
J Mol Neurosci 2003
PMID:Polymorphism of angiotensin-converting enzyme, angiotensinogen, and apolipoprotein E genes in Korean patients with cerebral infarction. 1450 Sep 90

Tumor necrosis factor (TNF) is an important cytokine in the inflammation process of atherosclerosis. Two biallelic polymorphisms in the TNF-alpha (TNF-alpha -308) and TNF-beta (TNF-beta +252) genes have been reported to be associated with TNF production and susceptibility to inflammatory diseases. We investigated two genetic polymorphisms in the TNF locus (TNF-alpha -308 G-->A and TNF-beta +252 A-->G) as risk factors for cerebral infarction (CI) by determining its prevalence in 294 survivors of CI, and in 581 age-, gender-, and race-matched controls. A significant association was found for the TNF-alpha and TNF-beta genotypes in CI patients compared with controls. A significant increase was found for the TNF-alpha A allele in controls compared with CI patients (chi2 = 7.593, p = 0.006, odds ratio = 1.74, confidence interval = 1.17-2.59). In addition, the TNF-alpha GG genotype increased the relative risk for CI in subjects with the TNF-beta AA genotype (chi2 = 4.998, p = 0.025). As a result, compared to controls, the frequency of the TNF-alpha AA genotype was decreased, whereas that of TNF-beta AA was increased in CI patients. The former implies an association with resistance, whereas the latter suggests an association with susceptibility to the disease. These results show that the TNF-alpha -308 and TNF-beta +252 locus plays an important role in the etiopathogenesis of CI.
J Mol Neurosci 2003
PMID:TNF-alpha and TNF-beta gene polymorphisms in cerebral infarction. 1459 15

Although edaravone (3-methyl-1-phenyl-pyrazolin-5-one), a newly developed radical scavenging agent, has been widely used for protection against ischemia-reperfusion (I-R) injury in patients with cerebral infarction, its effects on gastrointestinal I-R injury have not been evaluated. In the present study, we examined the effects of edaravone on experimental intestinal I-R damage in rats. In male Wistar rats with and without edaravone treatment, intestinal damage was induced by clamping the superior mesenteric artery for 30 min, followed by reperfusion. Edaravone was administered via intravenous infusion at 5 min before reperfusion was achieved by removal of the clamp. The rats were sacrificed after 60 min of reperfusion. Luminal protein and hemoglobin concentrations were measured as an index of mucosal injury and histological examination of hematoxylin and eosin-stained sections was performed. Thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity were measured in the mucosa as indicators of lipid peroxidation and neutrophil infiltration, respectively. The mucosal concentration of cytokine-induced neutrophil chemoattractant (CINC)-1 (a member of the IL-8 family) was determined by enzyme-linked immunosorbent assay (ELISA). Additionally, CINC-1 messenger RNA (mRNA) was measured by the reverse-transcription polymerase chain reaction (RT-PCR). As a result, the levels of luminal protein and hemoglobin, TBA-reactive substances, and MPO activity were all increased significantly by I-R injury, and these increases were significantly inhibited by treatment with edaravone. Multiple erosions and bleeding were observed macroscopically after the small intestine was exposed to I-R injury, and these changes were inhibited by administration of edaravone. Microscopic I-R damage was also reduced by treatment with edaravone. CINC-1 protein and CINC-1 mRNA were both increased by I-R injury, while edaravone markedly reduced the levels of both protein and mRNA. In summary, these results suggest that edaravone can protect the small intestine against I-R injury by scavenging oxygen-derived free radicals.
Int J Mol Med 2004 Jan
PMID:Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats. 1465 79


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