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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2015     Display Documents



  history
ID: 711853.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2015
Niacin activates the PI3K/Akt cascade via PKC- and EGFR-transactivation-dependent pathways through hydroxyl-carboxylic acid receptor 2
Authors:Sun, H.; Li, G.; Zhang, W.; Zhou, Q.; Yu, Y.; Shi, Y.; Offermanns, S.; Lu, J.; Zhou, N.
Date of Publication (YYYY-MM-DD):2014
Title of Journal:PLoS ONE
Volume:9
Issue / Number:11
Start Page:e112310
Audience:Not Specified
Abstract / Description:Niacin has been demonstrated to activate a PI3K/Akt signaling cascade to prevent brain damage after stroke and UV-induced skin damage; however, the underlying molecular mechanisms for HCA2-induced Akt activation remain to be elucidated. Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA2 receptors, we first demonstrated that niacin induced a robust Akt phosphorylation at both Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min and a subsequent reduction to baseline by 30 min through HCA2, and that the activation was significantly blocked by pertussis toxin. The HCA2-mediated activation of Akt was also significantly inhibited by the PKC inhibitors GF109203x and Go6983 in both cell lines, by the PDGFR-selective inhibitor tyrphostin A9 in CHO-HCA2 cells and by the MMP inhibitor GM6001 and EGFR-specific inhibitor AG1478 in A431 cells. These results suggest that the PKC pathway and PDGFR/EGFR transactivation pathway play important roles in HCA2-mediated Akt activation. Further investigation indicated that PI3K and the Gbetagamma subunit were likely to play an essential role in HCA2-induced Akt activation. Moreover, Immunobloting analyses using an antibody that recognizes p70S6K1 phosphorylated at Thr389 showed that niacin evoked p70S6K1 activation via the PI3K/Akt pathway. The results of our study provide new insight into the signaling pathways involved in HCA2 activation.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:MPI für Herz- und Lungenforschung
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang, China; Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China. College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang, China. Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany. %^ 1435822116
Identifiers:ISSN:1932-6203 (Electronic) 1932-6203 (Linking) %R 10.1371/journal.pone.0112310
URL:http://www.ncbi.nlm.nih.gov/pubmed/25375133
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