Abstract
Angiotensin (Ang) III is a biologically active metabolite of Ang II with similar effects and receptor binding properties as Ang II. Most Ang III studies delineate physiological effects of the peptide but, the intracellular pathways leading to the actions are unknown and are a focus of ongoing studies in the laboratory. Recently, we showed that Ang III induces mitogen activated protein kinases and astrocyte growth in a similar manner as Ang II. In these studies, we investigated in cultured brainstem rat astrocytes whether Ang III stimulates signal transducer and activators of transcription (STAT) 3. STAT3 is an important link between activation of the AT1 receptor and nuclear transcriptional changes leading to cell growth. Ang III significantly stimulated STAT3 in a dose- and time-dependent manner. The maximal stimulation occurred with 100 nM Ang III. This stimulation occurred as early as 1 minute, and was sustained for at least 15 minutes. Ang III induction of STAT3 occurred via stimulation of the Ang AT1 receptor, since pretreatment with 10 M Losartan, a selective AT1 receptor blocker, prevented Ang III-induced STAT3 phosphorylation. The selective AT2 Ang receptor blocker PD123319 was ineffective. These findings suggest that Ang III has similar effects as Ang II in astrocytes since it rapidly stimulates the phosphorylation of STAT3 through activation of the AT1 receptor. These studies are important in establishing signaling pathways for Ang III and provide validation of the central role of Ang III. (Support NSU PFDRG).
Faculty Sponsors
Michelle A. Clark
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-13-2012 1:00 PM
End Date
4-13-2012 5:30 PM
Angiotensin III Induced STAT3 Phosphorylation in Cultured Rat Astrocytes
Alvin Sherman Library
Angiotensin (Ang) III is a biologically active metabolite of Ang II with similar effects and receptor binding properties as Ang II. Most Ang III studies delineate physiological effects of the peptide but, the intracellular pathways leading to the actions are unknown and are a focus of ongoing studies in the laboratory. Recently, we showed that Ang III induces mitogen activated protein kinases and astrocyte growth in a similar manner as Ang II. In these studies, we investigated in cultured brainstem rat astrocytes whether Ang III stimulates signal transducer and activators of transcription (STAT) 3. STAT3 is an important link between activation of the AT1 receptor and nuclear transcriptional changes leading to cell growth. Ang III significantly stimulated STAT3 in a dose- and time-dependent manner. The maximal stimulation occurred with 100 nM Ang III. This stimulation occurred as early as 1 minute, and was sustained for at least 15 minutes. Ang III induction of STAT3 occurred via stimulation of the Ang AT1 receptor, since pretreatment with 10 M Losartan, a selective AT1 receptor blocker, prevented Ang III-induced STAT3 phosphorylation. The selective AT2 Ang receptor blocker PD123319 was ineffective. These findings suggest that Ang III has similar effects as Ang II in astrocytes since it rapidly stimulates the phosphorylation of STAT3 through activation of the AT1 receptor. These studies are important in establishing signaling pathways for Ang III and provide validation of the central role of Ang III. (Support NSU PFDRG).
