Document Detail


Molecular chaperone function for myocilin.
MedLine Citation:
PMID:  21873671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Myocilin is thought to be a stress response protein, but its exact molecular functions have not been established. Studies were conducted to see whether myocilin can act as a general molecular chaperone.
METHODS: Myocilin was isolated and purified from porcine trabecular meshwork (TM) cell culture media. Its ability to protect citrate synthase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the restriction endonuclease DrdI from thermal inactivation was evaluated. Light scattering was used to evaluate thermally induced aggregation of citrate synthase. Myocilin induction was assessed after exposure of TM cells to several types of stress treatments.
RESULTS: Levels of extracellular myocilin expressed by TM cells were increased in response to mechanical stretch, heat shock, TNFα, or IL-1α. Myocilin protected citrate synthase activity against thermal inactivation for 5 minutes at 55°C in a concentration-dependent manner, with nearly full protection of 1.5 μM citrate synthase in the presence of 650 nM myocilin. Myocilin significantly reduced thermal aggregation of citrate synthase to levels 36% to 44% of control levels. Myocilin also protected GAPDH from thermal inactivation for 10 minutes at 45°C. Myocilin at 18 nM was more effective than 1 μM bovine serum albumin at protecting DrdI from thermal inactivation.
CONCLUSIONS: Myocilin is induced in response to several cellular stresses and displays general molecular chaperone activity by protecting DrdI, citrate synthase, and GAPDH from thermal inactivation. Myocilin also suppresses the thermal aggregation of citrate synthase. One function of myocilin may be to serve as a molecular chaperone.
Authors:
Ann Marie Anderssohn; Kalani Cox; Kevin O'Malley; Scott Dees; Mojgan Hosseini; Lacey Boren; Anthony Wagner; John M Bradley; Mary J Kelley; Ted S Acott
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-29
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  52     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-30     Completed Date:  2011-12-13     Revised Date:  2012-03-05    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7548-55     Citation Subset:  IM    
Affiliation:
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cells, Cultured
Citrate (si)-Synthase / metabolism
Cytoskeletal Proteins / physiology*
Deoxyribonucleases, Type II Site-Specific / metabolism
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors
Eye Proteins / physiology*
Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating) / metabolism
Glycoproteins / physiology*
Hot Temperature
Molecular Chaperones / physiology*
Stress, Mechanical
Stress, Physiological
Swine
Trabecular Meshwork / metabolism*
Grant Support
ID/Acronym/Agency:
EY003279/EY/NEI NIH HHS; EY008247/EY/NEI NIH HHS; EY010572/EY/NEI NIH HHS; P30 EY010572-18/EY/NEI NIH HHS; R01 EY008247-23/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Cytoskeletal Proteins; 0/Enzyme Inhibitors; 0/Eye Proteins; 0/Glycoproteins; 0/Molecular Chaperones; 0/trabecular meshwork-induced glucocorticoid response protein; EC 1.2.1.13/Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating); EC 2.3.3.1/Citrate (si)-Synthase; EC 3.1.21.-/endodeoxyribonuclease DrdI; EC 3.1.21.4/Deoxyribonucleases, Type II Site-Specific

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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