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Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

Jia X, Chang T, Wilson TW, Wu L - PLoS ONE (2012)

Bottom Line: The effects of MG on diabetes and hypertension have been long recognized.The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells.The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Collage of Medicine, University of Saskatchewan, Saskatoon, Canada.

ABSTRACT
Methylglyoxal (MG) is a highly reactive metabolite physiologically presented in all biological systems. The effects of MG on diabetes and hypertension have been long recognized. In the present study, we investigated the potential role of MG in obesity, one of the most important factors to cause metabolic syndrome. An increased MG accumulation was observed in the adipose tissue of obese Zucker rats. Cell proliferation assay showed that 5-20 µM of MG stimulated the proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells. The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6. In summary, our study revealed a previously unrecognized effect of MG in stimulating adipogenesis by up-regulation of Akt signaling pathway and this mechanism might offer a new approach to explain the development of obesity.

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Effect of MG on p21, p-p21, p27, p-p27 and CDK2 activity in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of p21, p-21 and p27, p-p27 (A), and the activity of Cdk2 (B) were determined and compared. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments.
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pone-0036610-g005: Effect of MG on p21, p-p21, p27, p-p27 and CDK2 activity in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of p21, p-21 and p27, p-p27 (A), and the activity of Cdk2 (B) were determined and compared. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments.

Mentions: As Akt regulates cell growth by phosphorylating p21 and p27 [26], we further examined the effect of MG on p21 and p27 in 3T3-L1 cells (Fig. 5). Consistent with the increased phosphorylation of Akt1, phosphorylated p21 (p-p21) and p27 (p-p27) were also observed in 10 µM MG treated 3T3-L1 cells (Fig. 5A), indicating a role of MG in stimulating Akt1 signaling. Co-administration of SH-6 (10 µM) or alagebrium (50 µM) significantly prevented the increased phosphorylation of p21 and p27 induced by MG.


Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1.

Jia X, Chang T, Wilson TW, Wu L - PLoS ONE (2012)

Effect of MG on p21, p-p21, p27, p-p27 and CDK2 activity in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of p21, p-21 and p27, p-p27 (A), and the activity of Cdk2 (B) were determined and compared. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351465&req=5

pone-0036610-g005: Effect of MG on p21, p-p21, p27, p-p27 and CDK2 activity in 3T3-L1 cells.After 24 h treatment with or without MG (10 µM) in the presence or absence of SH-6 (10 µM)/alagebrium (50 µM), the protein levels of p21, p-21 and p27, p-p27 (A), and the activity of Cdk2 (B) were determined and compared. *P<0.05 vs control (CT) cells; +P<0.05 vs MG treated cells. The results were based on data from three experiments.
Mentions: As Akt regulates cell growth by phosphorylating p21 and p27 [26], we further examined the effect of MG on p21 and p27 in 3T3-L1 cells (Fig. 5). Consistent with the increased phosphorylation of Akt1, phosphorylated p21 (p-p21) and p27 (p-p27) were also observed in 10 µM MG treated 3T3-L1 cells (Fig. 5A), indicating a role of MG in stimulating Akt1 signaling. Co-administration of SH-6 (10 µM) or alagebrium (50 µM) significantly prevented the increased phosphorylation of p21 and p27 induced by MG.

Bottom Line: The effects of MG on diabetes and hypertension have been long recognized.The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells.The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Collage of Medicine, University of Saskatchewan, Saskatoon, Canada.

ABSTRACT
Methylglyoxal (MG) is a highly reactive metabolite physiologically presented in all biological systems. The effects of MG on diabetes and hypertension have been long recognized. In the present study, we investigated the potential role of MG in obesity, one of the most important factors to cause metabolic syndrome. An increased MG accumulation was observed in the adipose tissue of obese Zucker rats. Cell proliferation assay showed that 5-20 µM of MG stimulated the proliferation of 3T3-L1 cells. Further study suggested that accumulated-MG stimulated the phosphorylation of Akt1 and its targets including p21 and p27. The activated Akt1 then increased the activity of CDK2 and accelerated the cell cycle progression of 3T3-L1 cells. The effects of MG were efficiently reversed by advanced glycation end product (AGE) breaker alagebrium and Akt inhibitor SH-6. In summary, our study revealed a previously unrecognized effect of MG in stimulating adipogenesis by up-regulation of Akt signaling pathway and this mechanism might offer a new approach to explain the development of obesity.

Show MeSH
Related in: MedlinePlus