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Signaling Pathways Implicated in Butyrate‐Arrested Vascular Smooth Muscle Cell Proliferation
Author(s) -
Mathew Omana P,
Ranganna Kasturi,
Selvam Chelliah,
Yousefipour Zivar
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb167
Subject(s) - pi3k/akt/mtor pathway , butyrate , microbiology and biotechnology , protein kinase b , cell growth , signal transduction , phosphorylation , p70 s6 kinase 1 , biology , ribosomal s6 kinase , histone deacetylase , chemistry , histone , biochemistry , fermentation , gene
Prevalence and relevance of epigenetic components in cardiovascular disease pathways including those associated with atherosclerosis are now being explored to understand their impact on the pathogenesis. Butyrate, an epigenetic histone modifier with histone deacetylase (HDAC) inhibitory activity, inhibits vascular smooth muscle cells (VSMC) proliferation, an important component in the pathogenesis of atherosclerosis and alters cellular size and morphology. Since mTOR signaling pathways are crucial to cell proliferation, cell growth and survival by their multiple downstream pathways, here we investigate some of these pathways to understand the underlying mechanisms associated with butyrate effects on VSMC. Proliferating VSMC were exposed to 5 mM butyrate for different lengths of time and processed for assessing butyrate effects on the status of different signaling proteins by western analysis. Results indicate that butyrate treatment causes inhibition of mTOR expression and accordingly activation of mTOR by phosphorylation of Ser2448 is also inhibited. This inactivation of mTOR is further reflected in the inhibition of activation of its downstream effector p70S6 kinase, and in turn, inhibition of phosphorylation of p70S6 kinase substrate, S6 ribosomal protein, which are involved in the protein synthesis. Furthermore, butyrate treatment causes time‐dependent inhibition of PI3K, Akt/PKB and PDK1 activation by phosphorylation. The results indicate that inhibition of activation of both PI3K/Akt and mTOR pathways appear to be involved in butyrate arrested VSMC proliferation, which suggest that both pathways are interconnected and function as a single pathway in butyrate arrested VSMC proliferation because both pathways are crucial for the cell proliferation, cell growth and survival through the mediation of their downstream effectors. Support or Funding Information This study was made possible, in part, by Molecular Biology research infrastructure support from grant number 2G12MD007605 from the NIMHD/NIH”