Document Detail


Carnosine inhibits high glucose-induced mesangial cell proliferation through mediating cell cycle progression.
MedLine Citation:
PMID:  19154760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Huijie Jia; Xiaodan Qi; Shaohong Fang; Yuhong Jin; Xiaoying Han; Yi Wang; Aimin Wang; Hongbo Zhou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-25
Journal Detail:
Title:  Regulatory peptides     Volume:  154     ISSN:  0167-0115     ISO Abbreviation:  Regul. Pept.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-03     Completed Date:  2009-06-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  69-76     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, PR China.
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MeSH Terms
Descriptor/Qualifier:
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:
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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