title: Angiotensin II increased neuronal stem cell proliferation: role of AT2R.
abstract: Angiotensin II (Ang II), known a potent vasoactive substance in the renin-angiotensin system in the brain, plays a critical role in systemic blood pressure control. However, increasing evidence indicated that the physiological role of Ang II go beyond its vasoactive effect. In the present study, we demonstrated that Ang II type-1 receptor (AT1R) and type-2 receptor (AT2R) were expressed in primary rat hippocampal neuronal stem cells (NSCs). Treatment of rat hippocampal NSCs with Ang II increased cell proliferation. Pretreatment of NSCs with specific AT2R, but not AT1R, antagonist significantly suppressed Ang II-induced cell proliferation. Furthermore, Ang II stimulated ERK and Akt phosphorylation in NSCs. Pretreatment of MEK inhibitor, but not PI3K inhibitor, inhibited Ang II-induced ERK phosphorylation as well as cell proliferation. In addition, stimulation of NSCs with Ang II decreased expression of KV 1.2/KV 3.1 channels and blocked K(+) currents which lie downstream of ERK activation. Taken together, these findings underpin the role of AT2R as a novel target that regulates cell proliferation mediated by Ang II with implications for therapeutic intervention for regulation of neurogenesis.
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
authors.forename: Lie
authors.initials: L
authors.lastname: Gao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011945:Receptors, Angiotensin / Q000502:physiology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D015221:Potassium Channels; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases