| Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration. | |
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MedLine Citation:
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PMID: 17169845 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sanjoy K Bhattacharya; Manjunatha B Bhat; Hidenari Takahara |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Current eye research Volume: 31 ISSN: 0271-3683 ISO Abbreviation: Curr. Eye Res. Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-12-15 Completed Date: 2007-01-23 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8104312 Medline TA: Curr Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 1063-71 Citation Subset: IM |
Affiliation:
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Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA. SBhattacharya@med.miami.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / cytology, enzymology* Blotting, Western Calcium / metabolism Cells, Cultured Chelating Agents / pharmacology Child Egtazic Acid / analogs & derivatives, pharmacology Enzyme Inhibitors / pharmacology Fluorescent Antibody Technique, Indirect Humans Hydrolases / metabolism* Male Microscopy, Fluorescence Neurodegenerative Diseases / enzymology* Osmotic Pressure Rats Rats, Sprague-Dawley Thapsigargin / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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EY015266/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 3.5.3.15/protein-arginine deiminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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