Expression of signaling molecules associated with apoptosis in human ischemic stroke tissue.

2.50
Hdl Handle:
http://hdl.handle.net/10541/71978
Title:
Expression of signaling molecules associated with apoptosis in human ischemic stroke tissue.
Authors:
Mitsios, Nick; Gaffney, John; Krupinski, Jerzy; Mathias, Richard; Wang, Qiuyu; Hayward, Stuart; Rubio, Francisco; Kumar, Patricia; Kumar, Shant; Slevin, Mark
Abstract:
There is growing evidence that, because of the highly significant differences in gene activation/protein expression between animal models of stroke and stroke patients, the current treatment strategies based on animal stroke models have been unsuccessful. Therefore, it is imperative that the pathobiology of human stroke be studied. As a first step here, Western blotting and immunohistochemistry were employed to examine expression and tissue localization of key apoptotic proteins in infarct and peri-infarcted (penumbra) from grey and white matter in human postmortem tissue of 18 patients who died between 2 and 37 d after stroke caused by large vessel disease. The contralateral hemisphere was used as a control. JNK1, JNK2, and p53 were upregulated in the majority of samples, whereas Bcl-2, caspase-3, active caspase-3, phosphorylated p53 (p-p53), phosphorylated JNK1 (p-JNK1), and phosphorylated JNK2 (p-JNK2) were upregulated in approximately half of the samples. JNK1 expression was positively correlated with JNK2 expression in grey and white matter infarct and penumbra, whereas active caspase-3 levels were positively correlated with p-JNK2 levels in grey and white matter infarct. Using indirect immunoperoxidase staining of paraffin-embedded sections, active caspase-3 was found in infarcted neurons that co-localized with TUNEL-positive cells. p-JNK localization in the nuclei of TUNELpositive cells with the morphological appearance of neurons from infarct and penumbra was also demonstrated. The use of Kaplan Meier survival data demonstrated that the presence of Bcl-2 in penumbra of grey matter correlated significantly with shorter survival (p = 0.006). In conclusion, the present study has identified significantly altered expression of apoptotic proteins in human stroke tissue and shown that the presence of Bcl-2 in penumbra of grey matter has prognostic value. It is tempting to suggest that further studies of apoptotic proteins in human stroke may lead to identification of novel targets for drug discovery.
Affiliation:
Department of Biological Sciences, Manchester Metropolitan University, Chester St, Manchester M1 5GD, UK.
Citation:
Expression of signaling molecules associated with apoptosis in human ischemic stroke tissue. 2007, 47 (1):73-86 Cell Biochem. Biophys.
Journal:
Cell Biochemistry and Biophysics
Issue Date:
2007
URI:
http://hdl.handle.net/10541/71978
PubMed ID:
17406061
Type:
Article
Language:
en
ISSN:
1085-9195
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMitsios, Nick-
dc.contributor.authorGaffney, John-
dc.contributor.authorKrupinski, Jerzy-
dc.contributor.authorMathias, Richard-
dc.contributor.authorWang, Qiuyu-
dc.contributor.authorHayward, Stuart-
dc.contributor.authorRubio, Francisco-
dc.contributor.authorKumar, Patricia-
dc.contributor.authorKumar, Shant-
dc.contributor.authorSlevin, Mark-
dc.date.accessioned2009-06-30T14:24:33Z-
dc.date.available2009-06-30T14:24:33Z-
dc.date.issued2007-
dc.identifier.citationExpression of signaling molecules associated with apoptosis in human ischemic stroke tissue. 2007, 47 (1):73-86 Cell Biochem. Biophys.en
dc.identifier.issn1085-9195-
dc.identifier.pmid17406061-
dc.identifier.urihttp://hdl.handle.net/10541/71978-
dc.description.abstractThere is growing evidence that, because of the highly significant differences in gene activation/protein expression between animal models of stroke and stroke patients, the current treatment strategies based on animal stroke models have been unsuccessful. Therefore, it is imperative that the pathobiology of human stroke be studied. As a first step here, Western blotting and immunohistochemistry were employed to examine expression and tissue localization of key apoptotic proteins in infarct and peri-infarcted (penumbra) from grey and white matter in human postmortem tissue of 18 patients who died between 2 and 37 d after stroke caused by large vessel disease. The contralateral hemisphere was used as a control. JNK1, JNK2, and p53 were upregulated in the majority of samples, whereas Bcl-2, caspase-3, active caspase-3, phosphorylated p53 (p-p53), phosphorylated JNK1 (p-JNK1), and phosphorylated JNK2 (p-JNK2) were upregulated in approximately half of the samples. JNK1 expression was positively correlated with JNK2 expression in grey and white matter infarct and penumbra, whereas active caspase-3 levels were positively correlated with p-JNK2 levels in grey and white matter infarct. Using indirect immunoperoxidase staining of paraffin-embedded sections, active caspase-3 was found in infarcted neurons that co-localized with TUNEL-positive cells. p-JNK localization in the nuclei of TUNELpositive cells with the morphological appearance of neurons from infarct and penumbra was also demonstrated. The use of Kaplan Meier survival data demonstrated that the presence of Bcl-2 in penumbra of grey matter correlated significantly with shorter survival (p = 0.006). In conclusion, the present study has identified significantly altered expression of apoptotic proteins in human stroke tissue and shown that the presence of Bcl-2 in penumbra of grey matter has prognostic value. It is tempting to suggest that further studies of apoptotic proteins in human stroke may lead to identification of novel targets for drug discovery.en
dc.language.isoenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshApoptosis-
dc.subject.meshBrain-
dc.subject.meshBrain Ischemia-
dc.subject.meshCaspase 3-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation-
dc.subject.meshHumans-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.subject.meshSignal Transduction-
dc.subject.meshStroke-
dc.subject.meshTranscriptional Activation-
dc.titleExpression of signaling molecules associated with apoptosis in human ischemic stroke tissue.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biological Sciences, Manchester Metropolitan University, Chester St, Manchester M1 5GD, UK.en
dc.identifier.journalCell Biochemistry and Biophysicsen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.