Angiotensin II induction of AP-1 in neurons requires stimulation of PI3-K and JNK.
Angiotensin II (Ang II) acts via its type 1 (AT(1)) receptor in neurons to regulate the activity of multiple intracellular signaling molecules, including intracellular Ca(2+), protein kinase C, phosphatidylinositol 3-kinase (PI3-K), and c-Jun NH(2)-terminal kinase (JNK). The present studies investigated the upstream signaling molecules involved in the Ang II stimulation of activator protein-1 (AP-1) DNA binding in neurons. Treatment of neurons cultured from neonatal rat hypothalamus and brainstem with Ang II (100 nM) showed a time-dependent increase in AP-1 DNA binding and this effect was inhibited by the AT(1) receptor antagonist, losartan (1 microM), the PI3-K inhibitor, LY294002 (10 microM), and the JNK inhibitor, JNK inhibitor II (100 nM). Furthermore, Ang II (100 nM) causes a time-dependent increase in JNK activity which was attenuated by PI3-K inhibition. These data establish, for the first time, a signaling cascade involved in the Ang II activation of AP-1 DNA binding in neurons.
Fleegal
Melissa A
MA
Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610, USA.
Sumners
Colin
C
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018808:Transcription Factor AP-1; D000804:Angiotensin II; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases