Document Detail

Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration.
MedLine Citation:
PMID:  17169845     Owner:  NLM     Status:  MEDLINE    
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.
Sanjoy K Bhattacharya; Manjunatha B Bhat; Hidenari Takahara
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current eye research     Volume:  31     ISSN:  0271-3683     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-15     Completed Date:  2007-01-23     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1063-71     Citation Subset:  IM    
Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
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MeSH Terms
Astrocytes / cytology,  enzymology*
Blotting, Western
Calcium / metabolism
Cells, Cultured
Chelating Agents / pharmacology
Egtazic Acid / analogs & derivatives,  pharmacology
Enzyme Inhibitors / pharmacology
Fluorescent Antibody Technique, Indirect
Hydrolases / metabolism*
Microscopy, Fluorescence
Neurodegenerative Diseases / enzymology*
Osmotic Pressure
Rats, Sprague-Dawley
Thapsigargin / pharmacology
Grant Support
Reg. No./Substance:
0/Chelating Agents; 0/Enzyme Inhibitors; 139890-68-9/1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; 67-42-5/Egtazic Acid; 67526-95-8/Thapsigargin; 7440-70-2/Calcium; EC 3.-/Hydrolases; EC deiminase

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