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• W2023448182 startingPage "e112310" @default.
• W2023448182 abstract "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 Gβγ 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." @default.
• W2023448182 created "2016-06-24" @default.
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• W2023448182 date "2014-11-06" @default.
• W2023448182 modified "2023-10-14" @default.
• W2023448182 title "Niacin Activates the PI3K/Akt Cascade via PKC- and EGFR-Transactivation-Dependent Pathways through Hydroxyl-Carboxylic Acid Receptor 2" @default.
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• W2023448182 doi "https://doi.org/10.1371/journal.pone.0112310" @default.
• W2023448182 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4223033" @default.
• W2023448182 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25375133" @default.
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