ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes

Na Liu, George Stoica, Mingshan Yan, Virginia L. Scofield, Wenan Qiang, William S. Lynn, Paul K.Y. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm-/- astrocytes, like Atm-/- lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

Original languageEnglish (US)
Pages (from-to)1471-1480
Number of pages10
JournalLaboratory Investigation
Volume85
Issue number12
DOIs
StatePublished - Dec 1 2005

Keywords

  • Astrocyte
  • Ataxia telangiectasia mutated
  • Cerebellar Bergmann glia
  • Endoplasmic reticulum stress
  • Extracellular signal-regulated protein kinases
  • Oxidative stress

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Liu, N., Stoica, G., Yan, M., Scofield, V. L., Qiang, W., Lynn, W. S., & Wong, P. K. Y. (2005). ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes. Laboratory Investigation, 85(12), 1471-1480. https://doi.org/10.1038/labinvest.3700354