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Delayed but sustained induction of mitogen‐activated protein kinase activity is associated with β‐adrenergic receptor‐mediated morphological differentiation of astrocytes
Author(s) -
Gharami Kusumika,
Das Sumantra
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 - 10.1046/j.1471-4159.2003.02148.x
Subject(s) - mapk/erk pathway , protein kinase a , microbiology and biotechnology , kinase , mitogen activated protein kinase 3 , mitogen activated protein kinase , mitogen activated protein kinase kinase , biology , adrenergic receptor , mek inhibitor , signal transduction , receptor , propranolol , endocrinology , chemistry , medicine , biochemistry
Astroglial β‐adrenergic receptors (β‐ARs) are functionally linked to regulate cellular morphology. In primary cultures, the β‐AR agonist isoproterenol (ISP) can transform flat polygonal astrocytes into process‐bearing, mature stellate cells by 48 h, an effect that can be blocked by the β‐AR antagonist, propranolol. ISP induced immediate activation of protein kinase A (PKA) which persisted up to 2 h, with no visible change in cell morphology. However, activation of PKA was sufficient to drive the process of transformation to completion, suggesting the involvement of downstream regulators of PKA. In addition to PKA inhibitors, the mitogen‐activated protein kinase (MAPK) kinase inhibitor PD098059 also blocked ISP‐induced morphological transformation. ISP treatment resulted in a biphasic response of cellular phosphorylated MAPK (phosphorylated extracellular signal‐regulated kinase; p‐ERK) level: an initial decline in p‐ERK level followed by a sustained induction at 12–24 h, both of which were blocked by PKA inhibitor. The induction in pERK level coincided with initiation of morphological differentiation of the astrocytes and nuclear translocation of p‐ERK. A long‐lasting activation of p‐ERK activity by ISP, at a later stage, appears to be critical for the transformation of astrocytes.