Carnosine inhibits high glucose-induced mesangial cell proliferation through mediating cell cycle progression.
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.
Jia
Huijie
H
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, PR China.
Qi
Xiaodan
X
Fang
Shaohong
S
Jin
Yuhong
Y
Han
Xiaoying
X
Wang
Yi
Y
Wang
Aimin
A
Zhou
Hongbo
H
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002336:Carnosine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005562:Formazans / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D050527:Mesangial Cells / Q000378:metabolism*; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005562:Formazans; D013778:Tetrazolium Salts; D050760:Cyclin-Dependent Kinase Inhibitor p27; C079782:MTT formazan; D002336:Carnosine; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001973:Bromodeoxyuridine; D005947:Glucose