• Neuroscience · Sep 2014

    Glycoprotein nonmetastatic melanoma protein B (GPNMB) as a novel neuroprotective factor in cerebral ischemia-reperfusion injury.

    • Y Nakano, Y Suzuki, T Takagi, A Kitashoji, Y Ono, K Tsuruma, S Yoshimura, M Shimazawa, T Iwama, and H Hara.
    • Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu, Pharamaceutical University, Gifu 501-1196, Japan.
    • Neuroscience. 2014 Sep 26;277:123-31.

    AbstractGlycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein reported to have neuroprotective effects in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We investigated whether GPNMB is also neuroprotective against brain ischemia-reperfusion injury (IRI). Focal ischemia/reperfusion injury was induced via filament middle cerebral artery occlusion (MCAO) for 2h, followed by reperfusion upon withdrawal of the filament. We assessed the neuroprotective effects of GPNMB using transgenic (Tg) mice which over expressing GPNMB or recombinant GPNMB which has the sequence of human extracellular GPNMB. The results showed that GPNMB was up-regulated after IRI, and that genomic over-expression of GPNMB significantly ameliorated infarct volume. Next, we investigated the protective mechanisms of GPNMB via Western blotting and immunohistochemistry (IHC). Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and protein kinase B (Akt), were increased in the GPNMB Tg group according to Western blotting data. IHC analysis showed that GPNMB was expressed not only in neurons, but also in astrocytes, produced labeling patterns similar to that in human brain ischemia. Furthermore, recombinant GPNMB also decreased infarction volume. These results indicate that GPNMB protected neurons against IRI, and phosphor-Akt and phosphor-ERK might be a part of the protective mechanisms, and that the neuroprotective effect of GPNMB was seemingly induced by the extracellular sequence of GPNMB. In conclusion, these findings indicate that GPNMB has neuroprotective effects against IRI, via phosphorylation of ERK1/2 and Akt, suggesting that GPNMB may be a therapeutic target for ischemia-reperfusion injuries.Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…