Scientific Reports (Oct 2017)

A Novel β-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis

  • Victor García-González,
  • Jaime Mas-Oliva

DOI
https://doi.org/10.1038/s41598-017-13880-5
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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Abstract Our study tested the proposal that c-Myc activation in macrophages is differentially carried out dependent on the intracellular oxidative state of cells and potentially associated to the process of atherogenesis. Under our experimental conditions, the generation of reactive oxygen species carried out by the presence of oxidized low density lipoproteins (oxLDL) or Gram negative bacterial lipopolysaccharides (LPS) modifies the expression of cellular adhesion molecules such as c-Abl, calcium transport proteins such as the plasma membrane Ca2+-ATPase (PMCA), CD47, procaspase-7, CASP7, CHOP, transcriptional activators such as c-Jun and c-Myc and molecules that participate in the process of endocytosis like α- and β-adaptin. We present the first evidence showing that a state of oxidative stress alters c-Myc-dependent activity pathways in macrophages through binding to molecules such as β-adaptin promoting the reversible formation of a complex that presents the ability to regulate the development of the cell cycle. We propose that the subtle regulation carried out through the formation of this c-Myc/β-adaptin complex when cells change from a normal physiological condition to a state of oxidative stress, represents a defense mechanism against the deleterious effects caused by the loss of cell homeostasis.