Cell and Tissue Biology

, Volume 8, Issue 5, pp 374–383 | Cite as

The role of the MEK/ERK pathway in regulation of HDACI-induced senescence of transformed rat embryo fibroblasts

  • E. Yu. Kochetkova
  • T. V. Bykova
  • S. G. Zubova
  • T. V. Pospelova
Article
  • 45 Downloads

Abstract

A key regulator of cellular senescence, mTORC1 complex, is a target of many signaling cascades, including Ras/Raf/MEK/ERK cascade. In this paper, we investigated the role of the MEK/ERK branch of this cascade in the process of cellular senescence induced by sodium butyrate (NaBut), a histone deacetylase inhibitor (HDACI), in transformed rat-embryo fibroblasts. Suppression of MEK/ERK activity by inhibitor PD0325901 did not prevent activation of mTORC1 complex induced by NaBut treatment. Inhibition of MEK/ERK increased mTORC1 activity and activated mTORC2 complex. Activation of mTOR-containing complexes was accompanied by reorganization of the actin cytoskeleton (formation of actin stress fibers) and the appearance of cellular senescence markers. In contrast to NaBut-induced senescence, no protein accumulation was observed, probably due to increased activity of the degradation processes. Furthermore, senescence induction under suppression of MEK/ERK drastically decreased the cell viability, Thus, NaBut-induced senescence upon suppressed activity of the MEK/ERK branch of MAP kinase cascade has a more pronounced tumor-suppressing effect that is manifested by activation of both mTOR complexes, reorganization of the actin cytoskeleton and protein degradation.

Keywords

inhibitor of histone deacetylases sodium butyrate senescence-associated β-galactosidase 

Abbreviations

HDACI

histone deacetylase inhibitor

NaBut

sodium butyrate

SA-β-Gal

senescence-associated β-galactosidase

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Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • E. Yu. Kochetkova
    • 1
    • 2
  • T. V. Bykova
    • 1
  • S. G. Zubova
    • 1
  • T. V. Pospelova
    • 1
  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia
  2. 2.St. Petersburg State UniversitySt. PetersburgRussia

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