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Angiotensin III Induces c-Jun N-terminal Kinase Leading to Proliferation of Rat Astrocytes

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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 AT1 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 AT1 receptor antagonist, Losartan, prevented Ang III-induced JNK phosphorylation. Pretreatment of astrocytes with the AT2 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 AT1 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.

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Acknowledgments

This work was supported by a President’s Faculty Research & Development Grant from Nova Southeastern University. The authors would like to thank pharmacy students Larisa Odessky and Jenny Estrin for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL, 33328, USA

    Michelle A. Clark, Chinh Nguyen & Hieu Tran

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  1. Michelle A. Clark
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  2. Chinh Nguyen
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  3. Hieu Tran
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Correspondence to Michelle A. Clark.

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Clark, M.A., Nguyen, C. & Tran, H. Angiotensin III Induces c-Jun N-terminal Kinase Leading to Proliferation of Rat Astrocytes. Neurochem Res 37, 1475–1481 (2012). https://doi.org/10.1007/s11064-012-0738-9

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  • DOI: https://doi.org/10.1007/s11064-012-0738-9

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