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Activation of PKC isoforms by ATP/UTP and PMA in murine astrocytes
Author(s) -
Sun G. Y.,
Xu J.,
Liao Z.,
Lo SC.,
Weisman G. A.
Publication year - 2002
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 - 10.1046/j.1471-4159.81.s1.38_7.x
Subject(s) - protein kinase c , cytosol , microbiology and biotechnology , biology , phorbol , gene isoform , phospholipase c , astrocyte , kinase , biochemistry , signal transduction , enzyme , endocrinology , central nervous system , gene
Protein kinase C (PKC) isoforms are known to play an important role in regulating activities of a number of receptor signalling pathways. Our earlier studies have demonstrated that in murine astrocytes, PKC and mitogen‐activated protein kinases (MAPK) are involved in the stimulation of cytosolic phospholipase A2 and arachidonic acid (AA) release by extracellular nucleotides (ATP or UTP) and phorbol myristate acetate (PMA). These studies showed that PKC inhibitors or PKC down‐regulation induced by prolonged exposure to PMA had variable effects on AA release induced by ATP/UTP or PMA. PKC down‐regulation reduced PMA‐ but not ATP/UTP‐mediated AA release. In this study, we examined responses of PKC isoforms to stimulation by ATP/UTP and PMA in primary astrocytes isolated from mouse brain. These astrocytes showed 4 major PKC isoforms, namely, PKCα, ε, ι, and λ. Prolonged treatment of astrocytes with PMA resulted in down‐regulation of PKCα and ε, but not PKCι and λ. Separation of membrane and cytosol fractions revealed that PKCα was largely localized to the cytosol, PKCε in the membrane, whereas PKCι and λ were present in both membrane and cytosol fractions. Rapid translocation of PKCα from the cytosol to cell membrane could be observed in astrocytes treated with PMA, but not ATP or UTP. Neither PMA nor ATP altered cytosol and membrane distribution of PKCε, ι and λ. The lack of an effect of ATP and UTP on PKCα translocation suggests that nucleotide‐mediated AA release occurs by a PKCα‐independent mechanism. Acknowledgements: Supported by P01 AG 18357 from NIA.