| Effects of fungal statins on high-glucose-induced mouse mesangial cell hypocontractility may involve filamentous actin, t-complex polypeptide 1 subunit beta, and glucose regulated protein 78. | |
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MedLine Citation:
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PMID: 20627192 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glomerular hyperfiltration is associated with mesangial cell hypocontractility. How 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) influence mesangial cell contraction is unclear. We investigated the effect of statins on mesangial cell hypocontractility and identified candidate proteins and filamentous/globular (F/G)-actin involved in this process. A high-glucose-induced mouse mesangial cell hypocontractility model was treated with fungal statins, simvastatin (Sim), lovastatin (Lov), and pravastatin (Pra). The optimum statin dose was determined by an 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and then applied to a cell model. A 2-dimensional gel/matrix-assisted laser desorption/ionization time-of-flight mass spectrometer analysis was used to evaluate protein expression cells incubated in the presence of a normal level of glucose (N), a high level of glucose (H), and a high level of glucose plus Sim (H + S). Candidate proteins were analyzed. Finally, the ratio of F/G actin in groups N, H, and H+S was evaluated. The MTT assay showed that Sim and Lov exerted dose- and time-related inhibition of proliferation of mesangial cells at N, but Pra had no effect. The optimum doses selected for Sim was 1 microM and for Lov was 3 microM, which were 1 increment before significant proliferation inhibition. Both doses reversed cell hypocontractility significantly, but Sim was chosen for further proteomic and F/G actin analyses. Proteomic analysis of groups N, H, and H + S showed that 18 proteins were involved in hypocontractility. These proteins were grouped and analyzed based on their known functions. Two selected proteins, TCP-1beta and GRP78, that were upregulated and downregulated, respectively, were confirmed by Western blot and immunohistochemistry. In regard to the F/G actin, group H had a significantly lower ratio than that of group N, and group H + S returned to a level similar to that of group N. In conclusion, Sim and Lov both seem to reverse mesangial cell hypocontractility. The process of Sim reversal of mesangial cell hypocontractility may involve F-actin, TCP-1beta, and GRP78. |
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Authors:
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Jyh-Chang Hwang; Li-Chien Chang; Yuh-Feng Lin; Hao-Ai Shui; Jin-Shuen Chen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-19 |
Journal Detail:
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Title: Translational research : the journal of laboratory and clinical medicine Volume: 156 ISSN: 1878-1810 ISO Abbreviation: Transl Res Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-14 Completed Date: 2010-08-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101280339 Medline TA: Transl Res Country: United States |
Other Details:
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Languages: eng Pagination: 80-90 Citation Subset: AIM; IM |
Copyright Information:
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Copyright (c) 2010 Mosby, Inc. All rights reserved. |
Affiliation:
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Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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drug effects,
metabolism* Acyl Coenzyme A / metabolism Animals Cell Division / drug effects Glomerular Mesangium / cytology, drug effects, physiology* Glucose / pharmacology* Heat-Shock Proteins / drug effects, metabolism Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology Kidney Glomerulus / drug effects, physiology Lovastatin / pharmacology Mice Pravastatin / pharmacology Simvastatin / pharmacology* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tetradecanoylphorbol Acetate / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Acyl Coenzyme A; 0/Heat-Shock Proteins; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/molecular chaperone GRP78; 1553-55-5/3-hydroxy-3-methylglutaryl-coenzyme A; 16561-29-8/Tetradecanoylphorbol Acetate; 50-99-7/Glucose; 75330-75-5/Lovastatin; 79902-63-9/Simvastatin; 81093-37-0/Pravastatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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