TY - JOUR
T1 - Neurotrophic action of lipocortin 1 derived from astrocytes on cultured rat cortical neurons
AU - Mizuno, Haruo
AU - Asai, Kiyofumi
AU - Fujita, Kaori
AU - Uemura, Kenji
AU - Wada, Yoshiro
AU - Moriyama, Akihiko
AU - Ogawa, Hisamitsu
AU - Kimura, Shigeki
AU - Kato, Taiji
N1 - Funding Information:
This work was supported by the following sources: the Grant-in-Aid for Scientific Research on General Research (B) and on Priority Area, the Ministry of Education, Science, Sports and Culture, Japan, the Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare, Japan, and the Special Coordination Funds of the Science and Technology Agency of Japanese Government.
PY - 1998/9/18
Y1 - 1998/9/18
N2 - The lipocortins are a family of structurally related proteins, namely an annexin family, that exerts a variety of cellular functions through Ca2+-dependent binding to phospholipase A2 [EC 3.1.1.4], including a crucial role in the central nervous system (CNS) such as antipyrogenic, thermoregulatory and neuroprotective agents in vivo. To elucidate the paradigm of lipocortin 1 functions in the CNS, we have first demonstrated (1) the induction and subsequent extracellular secretion of LC1 by glucocorticoid in cultured rat astrocytes, and (2) neurotrophic activities (survival-promoting, neuritogenic and synaptogenic actions on rat cortical neurons) of recombinant LC1. Time-and dose-dependent experiments of a synthetic glucocorticoid, dexamethasone (DEX), on rat cortical astrocytes in culture revealed that the expression of the intracellular LC1 mRNA and protein were significantly augmented by DEX (1 μM). In addition, DEX evoked an extracellular secretion of LC1 without its cytotoxic effects. Furthermore, the recombinant LC1 appeared to promote not only the survival and neurite outgrowth but also the synaptogenesis of embryonal rat cortical neurons. These results suggest that LC1 induced and selectively released from astrocytes by either endogenously or exogenously introduced glucocorticoids may play a specific and essential role on development and regeneration of the central nervous system.
AB - The lipocortins are a family of structurally related proteins, namely an annexin family, that exerts a variety of cellular functions through Ca2+-dependent binding to phospholipase A2 [EC 3.1.1.4], including a crucial role in the central nervous system (CNS) such as antipyrogenic, thermoregulatory and neuroprotective agents in vivo. To elucidate the paradigm of lipocortin 1 functions in the CNS, we have first demonstrated (1) the induction and subsequent extracellular secretion of LC1 by glucocorticoid in cultured rat astrocytes, and (2) neurotrophic activities (survival-promoting, neuritogenic and synaptogenic actions on rat cortical neurons) of recombinant LC1. Time-and dose-dependent experiments of a synthetic glucocorticoid, dexamethasone (DEX), on rat cortical astrocytes in culture revealed that the expression of the intracellular LC1 mRNA and protein were significantly augmented by DEX (1 μM). In addition, DEX evoked an extracellular secretion of LC1 without its cytotoxic effects. Furthermore, the recombinant LC1 appeared to promote not only the survival and neurite outgrowth but also the synaptogenesis of embryonal rat cortical neurons. These results suggest that LC1 induced and selectively released from astrocytes by either endogenously or exogenously introduced glucocorticoids may play a specific and essential role on development and regeneration of the central nervous system.
UR - https://www.scopus.com/pages/publications/0032544384
UR - https://www.scopus.com/pages/publications/0032544384#tab=citedBy
U2 - 10.1016/S0169-328X(98)00163-6
DO - 10.1016/S0169-328X(98)00163-6
M3 - Article
C2 - 9748488
AN - SCOPUS:0032544384
SN - 0169-328X
VL - 60
SP - 28
EP - 39
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1
ER -