Changes in vimentin, lamin A/C and mitofilin induce aberrant cell organization in fibroblasts from Fanconi anemia complementation group A (FA-A) patients

Biochimie. 2013 Oct;95(10):1838-47. doi: 10.1016/j.biochi.2013.06.024. Epub 2013 Jul 2.

Abstract

Growing number of publication has proved an increasing of cellular function of the Fanconi anemia proteins. To chromosome stability and DNA repair new roles have been attributed to FA proteins in oxidative stress response and homeostasis, immune response and cytokines sensibility, gene expression. Our work shows a new role for FA-A protein: the organization of the cellular structure. By 2D-PAGE of FA-A and correct fibroblasts treated and untreated with H2O2 we identify different expression of protein involved in the structural organization of nucleus, intermediate filaments and mitochondria. Immunofluorescence and electronic microscopy analysis clearly show an already altered cellular structure in normal culture condition and this worsted after oxidative stress. FA-A cell appears structurally prone to physiologic stress and this could explain part of the phenotype of FA cells.

Keywords: 2D-PAGE; AML; BM; Cell structure; DSBs; ER; Fanconi anemia; GRP94; H(2)O(2); HSC; IFs; LMNA; N-acetyl cysteine; NAC; Oxidative stress; ROS; WB; acute myeloid leukemia; bone marrow; double strand breaks; endoplasmic reticulum; glucose response protein 94; human stem cells; hydrogen peroxide; intermediate filaments; lamin A; reactive oxygen species; two dimensional polyacrylamide gel electrophoresis; western blot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism*
  • Cytoskeleton / ultrastructure
  • Fanconi Anemia / genetics
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia / pathology
  • Fanconi Anemia Complementation Group A Protein / genetics
  • Fanconi Anemia Complementation Group A Protein / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Expression
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Microscopy, Electron
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Mutation
  • Oxidation-Reduction
  • Oxidative Stress
  • Vimentin / genetics
  • Vimentin / metabolism*

Substances

  • Fanconi Anemia Complementation Group A Protein
  • IMMT protein, human
  • LMNA protein, human
  • Lamin Type A
  • Mitochondrial Proteins
  • Muscle Proteins
  • Vimentin
  • Hydrogen Peroxide