Regulation of glial development by cystatin C.
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.
Hasegawa
Akiko
A
Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi, Japan.
Naruse
Masae
M
Hitoshi
Seiji
S
Iwasaki
Yasuno
Y
Takebayashi
Hirohide
H
Ikenaka
Kazuhiro
K
D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000166:cytology; D055316:Cystatin C; D015891:Cystatins / Q000276:immunology / Q000494:pharmacology*; D004622:Embryo, Mammalian; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D011480:Protease Inhibitors; C493393:Slc1a3 protein, mouse; C007293:DAPI; D020796:Receptor, Platelet-Derived Growth Factor alpha