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Characterization of the signal transduction pathways mediating noradrenaline‐stimulated MAPK activation and c‐fos expression in oligodendrocyte progenitors
Author(s) -
Khorchid Amani,
Larocca Jorge N.,
Almazan Guillermina
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19991215)58:6<765::aid-jnr4>3.0.co;2-0
Subject(s) - protein kinase c , wortmannin , mapk/erk pathway , pertussis toxin , bisindolylmaleimide , phospholipase c , ly294002 , signal transduction , protein kinase a , microbiology and biotechnology , biology , phorbol , kinase , chemistry , endocrinology , g protein , medicine , phosphatidylinositol
Abstract In examining the signaling transduction pathway of adrenoceptors in oligodendrocyte progenitors, we have found that stimulation of α 1 ‐adrenoceptors with norepinephrine (NE), in the presence of 3 μM propranolol, increased the activity of mitogen‐activated protein kinases (MAPKs). This stimulation was concentration‐ and time‐dependent, with maximal response after 10 min of exposure to 10 μM NE. Pertussis toxin (PTX) blocked NE‐mediated MAPK activation, suggesting that α 1 ‐adrenoceptor activates MAPK through a PTX‐sensitive G‐protein. In the presence of U73122, an inhibitor of phospholipase C (PLC), MAPK activation was blocked. In oligodendrocyte progenitor cultures, chronic treatment with phorbol‐12‐myristate‐13‐acetate (PMA) down‐regulated protein kinase C (PKC) and blocked NE‐mediated MAPK activation. The response to NE was also significantly decreased by the PKC inhibitors H7 and bisindolylmaleimide GF109203X. Similarly, the effect of NE on MAPK activation was not observed in a calcium‐free medium. Furthermore, attenuation of MAPK activity was observed when cultures were pretreated with LY294002 and wortmannin, inhibitors of phosphatidylinositol‐3 kinase (PI3K). These results suggest that α 1 ‐adrenoceptor‐mediated activation of MAPK involves a PTX‐sensitive G‐protein, PLC, PI3K, and 1,2‐diacyl glycerol (DAG)‐dependent PKC isozyme. Stimulation of oligodendrocyte progenitors with NE also resulted in an increase in c‐fos expression, which was mediated by both α 1 ‐ and β‐adrenoceptor and was calcium‐, PKC‐, and protein kinase A (PKA)‐dependent. Interestingly, in the presence of PD 098059, a specific inhibitor of MAPK kinase (MEK), both MAPK activity and c‐fos expression were blocked. This suggests that MAPK is implicated in the transmission of the signal from α 1 ‐adrenoceptor to c‐fos gene expression. J. Neurosci. Res. 58:765–778, 1999. © 1999 Wiley‐Liss, Inc.