Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration

Sanjoy K. Bhattacharya, Manjunatha B. Bhat, Hidenari Takahara

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Purpose: To demonstrate that elevated pressure increases the peptidyl arginine deiminase 2 (PAD2) expression in cultured astrocytes in vitro that can be modulated by pharmacological agents modulating intracellular calcium. Methods: Isolated rat brain astrocytes were subjected to pressure treatment. Western and immunohistochemical analyses detected PAD2 protein expression. Calcium measurements were achieved employing fluorescence-based microscopic imaging and quantification system. Experiments were repeated with human optic nerve head-derived astrocytes. Results: PAD2 has recently been shown to be associated with glaucomatous optic nerve. Astrocytes subjected to pressure (25-100 mmHg) show elevated level of PAD2, increased intracellular calcium, and concomitant citrullination but not significant cell death. PAD2 expression in response to elevated pressure may play a role in glaucomatous neurodegeneration. Pressure-treated astrocytes were also subjected to thapsigargin (50-250 nM) treatment, but it is unclear whether this had any further effect in increasing PAD2 expression. Conversely, treatment with calcium chelating agent BAPTA-AM (50-250 nM) results in decreased intracellular calcium concentration and PAD2. Conclusions: These results suggest calcium modulation could be exploited as therapeutic strategy to modulate pressure-induced PAD2 expression and citrullination.

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalCurrent Eye Research
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2006

Keywords

  • Citrullination
  • Elevated intraocular pressure
  • Glaucoma
  • Optic nerve damage
  • Peptidyl arginine deiminase 2

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

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