کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10956743 | 1099444 | 2007 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Nitric oxide (NO) and peroxynitrite, which are produced by activated microglia, are responsible for accelerated neurodegeneration in cathepsin D-deficient (CDâ/â) mice. To elucidate the mechanisms by which microglia are initially activated in CDâ/â mice, we analyzed the possible relationship between lysosomal storage and microglial activation. In CDâ/â mice, the microglial NO-generating activity that was closely associated with the induction of inducible NO synthase and the cationic amino acid transporter-2 (CAT-2) coincided well with the lysosomal storage of subunit c of mitochondrial F0F1ATPase and the formation of ceroid/lipofuscin. Furthermore, activated microglia, which are often accumulating subunit c and ceroid/lipofuscin, showed proliferation activity and an activation of p38 mitogen-activated protein (MAP) kinase. In the primary cultured microglia, pepstatin A was found to enhance the generation of NO and superoxide anion radicals. In these pepstatin A-treated microglia, both an increased generation of the intracellular reactive oxygen species (ROS) and an activation of p38 MAP kinase were observed. These results suggest that the ceroid/lipofuscin which form in microglia activate the p38 MAP kinase cascade through the increased intracellular generation of ROS in CDâ/â mice. The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 35, Issue 4, August 2007, Pages 573-584
Journal: Molecular and Cellular Neuroscience - Volume 35, Issue 4, August 2007, Pages 573-584
نویسندگان
Ryo Yamasaki, Jian Zhang, Ichiro Koshiishi, Dewi F. Sastradipura Suniarti, Zhou Wu, Christoph Peters, Michael Schwake, Yasuo Uchiyama, Jun-ichi Kira, Paul Saftig, Hideo Utsumi, Hiroshi Nakanishi,