Implications of protease M/neurosin in myelination during experimental demyelination and remyelination.
Protease M/neurosin is a serine protease expressed by oligodendrocytes (OLGs) in the central nervous system (CNS). To investigate the role of protease M/neurosin during experimental demyelination and remyelination, mice were fed cuprizone (bis-cyclohexanon oxaldihydrazone). Semi-quantitative RT-PCR analysis and immunohistochemistry revealed that the expressions of protease M/neurosin mRNA and protein were rapidly reduced in demyelination, whereas the expression of protease M/neurosin was increased in pi form of glutathione-S-transferases (GST-pi)-positive OLGs during remyelination. Cultured primary OLGs displayed a strong correlation between protease M/neurosin and myelin basic protein (MBP). After tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma stimulation, these proteins showed colocalization in the oligodendroglial process. The suppression of protease M/neurosin using RNAi reduced the level of MBP mRNA in cultured OLGs. In contrast, the reduced level of protease M/neurosin was not associated with oligodendroglial cell death or differentiation in cultured OLGs. This study identifies that protease M/neurosin in OLGs is closely associated with the expression of the MBP and the PLP gene. Our data emphasize that the maintenance of myelination is an important function of protease M/neurosin in OLGs, suggesting its relation to the oligodendroglial response to myelin disorders.
Bando
Yoshio
Y
Department of Functional Anatomy and Neuroscience, Asahikawa Medical College, Asahikawa, Hokkaido 078-8510, Japan. ybando@asahikawa-med.ac.jp
Ito
Shinji
S
Nagai
Yoshiko
Y
Terayama
Ryuji
R
Kishibe
Mari
M
Jiang
Ying-Ping
YP
Mitrovic
Branka
B
Takahashi
Takayuki
T
Yoshida
Shigetaka
S
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000494:pharmacology; D007610:Kallikreins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D003471:Cuprizone; D007371:Interferon-gamma; D051549:Glutathione S-Transferase pi; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D007610:Kallikreins; C491223:Prss18 protein, mouse