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PGF2α-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN
MIIR Faculty Research
  • Kevin M. Rice, Marshall University
  • Sreevani Uddemarri, Marshall University
  • Devashish H. Desai, Marshall University
  • Ryan G. Morrison, Marshall University
  • R. Harris, Marshall University
  • Eric R. Blough, Marshall University
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Prostaglandin F2α (PGF2α) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2α –induced VSMC hypertrophy we examined the ability of the PGF2α analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6k), glycogen synthase kinase-3β (GSK-3β), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3β, PTEN and ERK1/2 but not JNK phosphorylation. Whereas inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 blocked fluprostenol-induced changes in total protein content, pretreatment with rapamycin or with the ERK1/2-MAPK inhibitor UO126 did not. Taken together, these findings suggest that fluprostenol-induced changes in A7R5 hypertrophy involve mTOR translocation and occur through PI3K-dependent mechanisms.

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The authors’ accepted manuscript is freely available from PubMed Central at DOI: 10.1016/j.prostaglandins.2007.10.009.

Copyright © 2007 Elsevier Inc. All rights reserved.

Citation Information
Rice, K. M., Uddemarri, S., Desai, D. H., Morrison, R. G., Harris, R., Wright, G. L., & Blough, E. R. (2008). PGF(2alpha)-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70(S6k), and PTEN. Prostaglandins & Other Lipid Mediators, 85(1):49-57.