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From the nucleus to the plasma membrane: translocation of the nuclear proteins histone H3 and lamin B1 in apoptotic microglia

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Abstract

Nuclear autoantibodies have been found in patients with autoimmune diseases. One possible source for nuclear antigens are apoptotic cells. However, the mechanism of how apoptotic cells make nuclear factors accessible to the immune system is still elusive. In the present study, we investigated the redistribution of nuclear components after UV irradiation in the microglial cell line BV-2 and in primary mouse microglia at the ultrastructural level. We used transmission electron microscopy-coupled electron energy loss spectroscopy (EELS) to measure phosphorus as an indicator for nucleic acids and immunogold labeling to detect histone H3 and lamin B1 in apoptotic cells. EELS revealed elevated concentrations of phosphorus in nuclear and cytoplasmic condensed chromatin compared to the remaining cytoplasm. Furthermore, immunolabeling of lamin B1 and histone H3 was detected in apoptotic microglia not only in the nucleus, but also in the cytoplasm, and even at the plasma membrane. Confocal images of apoptotic microglia, which were not previously permeabilized, showed patches of histone H3 and lamin B1 labeling at the cell surface. The pan-caspase inhibitor Z-VAD-FMK (carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone) prevented the occurrence of cytoplasmic condensed chromatin in apoptotic microglia. Our findings indicate that nuclear components leak from the nucleus into the cytoplasm in apoptotic microglia. At least histone H3 and lamin B1 reach the cell surface, this may promote autoreactive processes.

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Acknowledgments

B.K. was funded in part by the European Union’s Seventh Framework Programme (FP7/2007-2013) under Grant agreement no HEALTH-F2-2011-278850 (INMiND).

Author information

Authors and Affiliations

  1. Department of Cell Biology, University of Salzburg, Hellbrunnerstraße 34, 5020, Salzburg, Austria

    Barbara Klein, Ursula Lütz-Meindl & Hubert H. Kerschbaum

  2. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria

    Barbara Klein

  3. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria

    Barbara Klein

Authors
  1. Barbara Klein
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  2. Ursula Lütz-Meindl
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  3. Hubert H. Kerschbaum
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Corresponding authors

Correspondence to Barbara Klein or Hubert H. Kerschbaum.

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10495_2014_970_MOESM1_ESM.tif

Supplementary material 1 (TIFF 283 kb) Time course of DNA laddering in BV-2 microglia after UV irradiation. Lane 1 marker (M), Lane 2 control (C); Lane 3–5 DNA of BV-2 cells 1, 3, or 5 h after UV irradiation

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Klein, B., Lütz-Meindl, U. & Kerschbaum, H.H. From the nucleus to the plasma membrane: translocation of the nuclear proteins histone H3 and lamin B1 in apoptotic microglia. Apoptosis 19, 759–775 (2014). https://doi.org/10.1007/s10495-014-0970-7

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  • DOI: https://doi.org/10.1007/s10495-014-0970-7

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