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Sphingosine 1‐phosphate induces the production of glial cell line‐derived neurotrophic factor and cellular proliferation in astrocytes
Author(s) -
Yamagata Kazuo,
Tagami Motoki,
Torii Yasuyoshi,
Takenaga Fumio,
Tsumagari Shigehisa,
Itoh Shingo,
Yamori Yukio,
Nara Yasuo
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10180
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , biology , astrocyte , neuroglia , sphingosine 1 phosphate , microbiology and biotechnology , cell culture , neurotrophin , growth factor , sphingosine , cell growth , nerve growth factor , endocrinology , medicine , central nervous system , biochemistry , receptor , genetics
Sphingosine 1‐phosphate (S1P) is a platelet‐derived bioactive sphingolipid that evokes a variety of biological responses. To understand the role of S1P in the central nervous system, we have examined the effect of S1P on the production of glial cell line‐derived neurotrophic factor (GDNF) and growth regulation of cortical astrocytes from rat embryo. Moreover, we examined the possibility that the expression of GDNF is regulated differently in cultured astrocytes from the stroke‐prone spontaneously hypertensive rat (SHRSP) than in those from Wistar kyoto rats (WKY). The mRNA expression was quantitated by RT‐PCR based on the fluorescent TaqMan methodology. A new instrument capable of measuring fluorescence in real time was used to quantify gene amplification in astrocytes. GDNF protein was investigated by enzyme‐linked immunosorbent assay. S1P induced the expression of GDNF mRNA and the production of GDNF protein in a dose‐dependent manner in WKY astrocytes. Moreover, S1P increased cell numbers and induced the proliferation of astrocytes. In addition, the level of mRNA expression and protein production of GDNF was significantly lower in SHRSP than WKY astrocytes following exposure to S1P. These findings revealed that S1P augments GDNF protein production and cellular growth in astrocytes. Also, our results indicate that production in SHRSP astrocytes was attenuated in response to S1P compared with that observed in WKY. We conclude that S1P specifically triggers a cascade of events that regulate the production of GDNF and cell growth in astrocytes. Our results also suggest that the reduced expression of GDNF caused by S1P is a factor in the stroke proneness of SHRSP. GLIA 41:199–206, 2003. © 2003 Wiley‐Liss, Inc.