Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration

Sanjoy K Bhattacharya, Manjunatha B. Bhat, Hidenari Takahara

Research output: Contribution to journalArticle

25 Citations (Scopus)

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

Fingerprint

Astrocytes
Pressure
Calcium
Thapsigargin
Optic Disk
Optic Nerve
arginine deiminase
Cell Death
Fluorescence
Pharmacology
Brain
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration. / Bhattacharya, Sanjoy K; Bhat, Manjunatha B.; Takahara, Hidenari.

In: Current Eye Research, Vol. 31, No. 12, 01.12.2006, p. 1063-1071.

Research output: Contribution to journalArticle

Bhattacharya, Sanjoy K ; Bhat, Manjunatha B. ; Takahara, Hidenari. / Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration. In: Current Eye Research. 2006 ; Vol. 31, No. 12. pp. 1063-1071.
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