| Carnosine inhibits high glucose-induced mesangial cell proliferation through mediating cell cycle progression. | |
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MedLine Citation:
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PMID: 19154760 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased mesangial cell proliferation is one of the major pathologic features in the early stage of diabetic nephropathy (DN). Carnosine is an endogenously synthesized dipeptide that has been reported as a protective factor in diabetic nephropathy. However, the underlying mechanism involved in this effect remains to be elucidated. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, the 5-bromo-2-deoxy-uridine (BrdU) cell proliferation assay, flow cytometry and western blotting. The results showed that pretreatment of mesangial cells with carnosine significantly inhibited cell proliferation and DNA synthesis in a dose-dependent manner by increasing the cell population in G1 and reducing that in S-phase. In addition, carnosine could reverse high glucose-induced down-regulation of cyclin-dependent kinase inhibitor p21 but not that of p27. Furthermore, carnosine could reduce the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK). Taken together, these results suggest that carnosine can inhibit mesangial cell proliferation by modulating cell cycle progress, indicating that carnosine could be a potential therapeutic agent for the prevention of DN in the early stage. |
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Authors:
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Huijie Jia; Xiaodan Qi; Shaohong Fang; Yuhong Jin; Xiaoying Han; Yi Wang; Aimin Wang; Hongbo Zhou |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-12-25 |
Journal Detail:
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Title: Regulatory peptides Volume: 154 ISSN: 0167-0115 ISO Abbreviation: Regul. Pept. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-03 Completed Date: 2009-06-22 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8100479 Medline TA: Regul Pept Country: Netherlands |
Other Details:
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Languages: eng Pagination: 69-76 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bromodeoxyuridine / metabolism Carnosine / pharmacology* Cell Cycle / drug effects* Cell Cycle Proteins / metabolism Cell Proliferation / drug effects* Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / metabolism Dose-Response Relationship, Drug Extracellular Signal-Regulated MAP Kinases / metabolism Formazans / metabolism Glucose / pharmacology* L-Lactate Dehydrogenase / metabolism Mesangial Cells / metabolism* Rats Tetrazolium Salts / metabolism Time Factors p38 Mitogen-Activated Protein Kinases / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Formazans; 0/Tetrazolium Salts; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 23305-68-2/MTT formazan; 305-84-0/Carnosine; 50-99-7/Glucose; 59-14-3/Bromodeoxyuridine; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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