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

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    Authors
    Mitsios, Nick
    Gaffney, John
    Krupinski, Jerzy
    Mathias, Richard
    Wang, Qiuyu
    Hayward, Stuart
    Rubio, Francisco
    Kumar, Patricia
    Kumar, Shant
    Slevin, Mark
    Affiliation
    Department of Biological Sciences, Manchester Metropolitan University, Chester St, Manchester M1 5GD, UK.
    Issue Date
    2007
    
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    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.
    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
    URI
    http://hdl.handle.net/10541/71978
    PubMed ID
    17406061
    Type
    Article
    Language
    en
    ISSN
    1085-9195
    Collections
    All Christie Publications

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