title: Angiotensin III induces c-Jun N-terminal kinase leading to proliferation of rat astrocytes.
abstract: Previously, we showed in cultured rat astrocytes that angiotensin (Ang) III induced astrocyte proliferation and phosphorylation of ERK1/2 mitogen activated protein (MAP) kinases through interaction with the AT(1) receptor. In the current study, we determined whether the c-Jun N terminal kinase (JNK) MAP kinase pathway was similarly affected by the peptide in cultured brainstem astrocytes. Ang III induced JNK phosphorylation in a concentration- and time-dependent manner. Similar to ERK1/2 phosphorylation, maximal phosphorylation occurred with 100 nM Ang III and was apparent within a minute of exposure to the peptide. Peak effects were observed over a 5-15 min time range. Pretreatment of brainstem astrocytes with the JNK inhibitor, SP600125, prevented Ang III phosphorylation of JNK, as well as Ang III-mediated astrocyte growth. The selective AT(1) receptor antagonist, Losartan, prevented Ang III-induced JNK phosphorylation. Pretreatment of astrocytes with the AT(2) receptor blocker PD123319 was ineffective in preventing JNK phosphorylation by Ang III. Interestingly, both Ang II and Ang III induced JNK phosphorylation to a similar extent suggesting that the two peptides were equipotent in this effect. Our findings suggest that Ang III interacts with Ang AT(1) receptors to directly stimulate the JNK MAP kinase pathway leading to astrocyte growth. This study is the first to show that Ang III actions may involve the JNK MAP kinase pathway in astrocytes and provide key information that may lead to a better understanding of the functions of Ang III in the central nervous system, in particular in astrocytes.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA. miclark@nova.edu
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Clark
authors.forename: Chinh
authors.initials: C
authors.lastname: Nguyen
authors.forename: Hieu
authors.initials: H
authors.lastname: Tran
mesh_terms: D000805:Angiotensin III / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation; D005260:Female; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000805:Angiotensin III