Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice

Yamasaki R, Zhang J, Koshiishi I, Sastradipura Suniarti DF, Wu Z, Peters C, Schwake M, Uchiyama Y, Kira J-ichi, Saftig P, Utsumi H, et al. (2007)
Molecular and Cellular Neuroscience 35(4): 573-584.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Yamasaki, Ryo; Zhang, Jian; Koshiishi, Ichiro; Sastradipura Suniarti, Dewi F.; Wu, Zhou; Peters, Christoph; Schwake, MichaelUniBi ; Uchiyama, Yasuo; Kira, Jun-ichi; Saftig, Paul; Utsumi, Hideo; Nakanishi, Hiroshi
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Abstract / Bemerkung
Nitric oxide (NO) and peroxynitrite, which are produced by activated microglia, are responsible for accelerated neurodegeneration in cathepsin D-deficient (CD−/−) mice. To elucidate the mechanisms by which microglia are initially activated in CD−/− mice, we analyzed the possible relationship between lysosomal storage and microglial activation. In CD−/− 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 CD−/− mice. The activated p38 MAP kinase cascade then promotes the expression of iNOS and CAT-2, thereby inducing the overproduction of NO.
Erscheinungsjahr
2007
Zeitschriftentitel
Molecular and Cellular Neuroscience
Band
35
Ausgabe
4
Seite(n)
573-584
ISSN
10447431
Page URI
https://pub.uni-bielefeld.de/record/2953351

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Yamasaki R, Zhang J, Koshiishi I, et al. Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Molecular and Cellular Neuroscience. 2007;35(4):573-584.
Yamasaki, R., Zhang, J., Koshiishi, I., Sastradipura Suniarti, D. F., Wu, Z., Peters, C., Schwake, M., et al. (2007). Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Molecular and Cellular Neuroscience, 35(4), 573-584. https://doi.org/10.1016/j.mcn.2007.05.002
Yamasaki, Ryo, Zhang, Jian, Koshiishi, Ichiro, Sastradipura Suniarti, Dewi F., Wu, Zhou, Peters, Christoph, Schwake, Michael, et al. 2007. “Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice”. Molecular and Cellular Neuroscience 35 (4): 573-584.
Yamasaki, R., Zhang, J., Koshiishi, I., Sastradipura Suniarti, D. F., Wu, Z., Peters, C., Schwake, M., Uchiyama, Y., Kira, J. -ichi, Saftig, P., et al. (2007). Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Molecular and Cellular Neuroscience 35, 573-584.
Yamasaki, R., et al., 2007. Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Molecular and Cellular Neuroscience, 35(4), p 573-584.
R. Yamasaki, et al., “Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice”, Molecular and Cellular Neuroscience, vol. 35, 2007, pp. 573-584.
Yamasaki, R., Zhang, J., Koshiishi, I., Sastradipura Suniarti, D.F., Wu, Z., Peters, C., Schwake, M., Uchiyama, Y., Kira, J.-ichi, Saftig, P., Utsumi, H., Nakanishi, H.: Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice. Molecular and Cellular Neuroscience. 35, 573-584 (2007).
Yamasaki, Ryo, Zhang, Jian, Koshiishi, Ichiro, Sastradipura Suniarti, Dewi F., Wu, Zhou, Peters, Christoph, Schwake, Michael, Uchiyama, Yasuo, Kira, Jun-ichi, Saftig, Paul, Utsumi, Hideo, and Nakanishi, Hiroshi. “Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in cathepsin D-deficient mice”. Molecular and Cellular Neuroscience 35.4 (2007): 573-584.
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