title: The effect of angiotensin II and IV on ERK1/2 and CREB signalling in cultured rat astroglial cells.
abstract: Angiotensin peptides produced by the brain renin-angiotensin system have established roles in cognition, but there is no mechanistic basis of angiotensin effects on memory. Astroglial cells present throughout the whole brain, synthesize all the components of the renin-angiotensin system and express angiotensin receptors; therefore our aim was to assess changes in intracellular signalling pathways related to memory formation, particularly the activation of CREB and ERK1/2 in astroglial cells grown in the presence of angiotensin peptides. Cultured rat astroglial cells were treated for 24 h with 10 microM angiotensin II and/or 10 microM angiotensin IV in the presence or absence of 100 microM losartan (AT1-receptor antagonist) or 100 microM PD123319 (AT2-receptor antagonist). Both angiotensin peptides alone were without effect on culture protein levels and cell viability and did not induce oxidative stress, but both peptides together slightly elevated cell growth rates and increased damaged, apoptotic cell numbers. This effect was most probably mediated by the AT1 receptor. Angiotensin II but not angiotensin IV increased intracellular calcium via activation of AT1 receptor. Angiotensin IV but not angiotensin II increased extracellular-regulated protein kinases 1 and 2 (ERK1/2) by 65% and T202, T204 phosphorylated ERK1/2 levels by 36%; this effect was blocked in part by both losartan and PD123319. Angiotensin II but not angiotensin IV increased cyclic AMP-responsive element binding protein (CREB) expression by almost 100% and elevated Ser 133-phosphorylated CREB levels by 56%. These effects were also inhibited in part by both losartan and PD123319. Our results indicate that CREB activation in cultured rat glial cells is mediated mostly by angiotensin II. Angiotensin IV appears to affect the ERK1/2 pathway.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15a, 15274 Bialystok, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Holownia
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Braszko
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D017362:Cyclic AMP Response Element-Binding Protein; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019808:Losartan