Premium
The protein phosphatase 1/2A inhibitor okadaic acid increases CREB and Elk‐1 phosphorylation and c‐ fos expression in the rat striatum in vivo
Author(s) -
Choe Eun Sang,
Parelkar Nikhil K.,
Kim Jong Yeon,
Cho Hyun Wook,
Kang Ho Sung,
Mao Limin,
Wang John Q.
Publication year - 2004
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.1471-4159.2003.02334.x
Subject(s) - okadaic acid , creb , striatum , phosphorylation , phosphatase , in vivo , chemistry , protein phosphatase 1 , medicine , microbiology and biotechnology , biochemistry , endocrinology , biology , dopamine , gene , transcription factor
Activation of group I metabotropic glutamate receptors (mGluRs) up‐regulates transcription factor cyclic AMP response element‐binding protein (CREB) and Elk‐1 phosphorylation via extracellular signal‐regulated kinase 1/2 (ERK1/2) in the striatum in vivo . Protein phosphatase 1/2A further regulates immediate early gene expression by inactivating (dephosphorylating) CREB. In this study, using semi‐quantitative immunohistochemical and western blot analyses and in situ hybridization histochemistry, we found that intrastriatal infusion of the protein phosphatase 1/2A inhibitor okadaic acid (0.005, 0.05 and 0.5 nmol) increased CREB and Elk‐1 phosphorylation and c‐Fos immunoreactivity in the injected dorsal striatum in a dose‐dependent manner. In addition, okadaic acid (0.05 and 0.5 n m ) increased c‐ fos mRNA expression in the dorsal striatum in a dose‐dependent manner. Intrastriatal infusion of the group I agonist 3,5‐dihydroxyphenylglycine (DHPG) at 100 and 250 n m also increased CREB and Elk‐1 phosphorylation. Pre‐treatment of okadaic acid (0.05 n m ) did not alter DHPG‐induced increases in the phosphorylation of the two transcription factors. These data suggest that protein phosphatase 1/2A in striatal neurons is tonically active in dephosphorylating CREB and Elk‐1 and thus suppressing constitutive c‐ fos mRNA and protein expression. Inhibition of the phosphatase 1/2A may contribute to the group I mGluR‐regulated phosphorylation of these transcription factors and c‐fos expression.