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Regulation of glial development by cystatin C
Author(s) -
Hasegawa Akiko,
Naruse Masae,
Hitoshi Seiji,
Iwasaki Yasuno,
Takebayashi Hirohide,
Ikenaka Kazuhiro
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04169.x
Subject(s) - astrocyte , cystatin c , glial fibrillary acidic protein , nestin , cystatin , neurosphere , neural stem cell , proteases , chemistry , microbiology and biotechnology , embryonic stem cell , biology , biochemistry , stem cell , immunology , immunohistochemistry , central nervous system , endocrinology , enzyme , adult stem cell , creatinine , gene
Abstract Cystatin C (CysC) is an endogenous cysteine proteases inhibitor produced by mature astrocytes in the adult brain. Previously we isolated CysC as a factor activating the glial fibrillary acidic protein (GFAP) promoter, and showed that CysC is expressed in astrocyte progenitors during development. Here we show that protease inhibitor activity increased daily in conditioned medium, and that this activity was mainly a result of CysC released from primary cultured cells. Human CysC added to the culture medium of primary brain cells increased the number of GFAP‐positive and nestin‐positive cells. Human CysC also increased the number of neurospheres formed from embryonic brain, and thus it increases the number of neural stem/precursor cells in a manner similar to glycosylated rat CysC. The addition of a neutralizing antibody, on the other hand, greatly decreased the number of GFAP and glutamate aspartate transporter (GLAST)‐positive astrocytes. This decrease was reversed by the addition of CysC but not by another cysteine protease inhibitor. Thus, the promotion of astrocyte development by CysC appears to be independent of its protease inhibitor activity. The antibody increased the number of oligodendrocytes and their precursors. Therefore, CysC modifies glial development in addition to its activity against neural stem/precursor cells.