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Sciadopitysin Alleviates Methylglyoxal-Mediated Glycation in Osteoblastic MC3T3-E1 Cells by Enhancing Glyoxalase System and Mitochondrial Biogenesis

Sciadopitysin Alleviates Methylglyoxal-Mediated Glycation in Osteoblastic MC3T3-E1 Cells by Enhancing Glyoxalase System and Mitochondrial Biogenesis

E M Choi, K S Suh, S Y Rhee, Y S Kim

Free Radic Res. 2014 Jul;48(7):729-39.

PMID: 24628445

Abstract:

Methylglyoxal (MG) is a precursor of advanced glycation end products, which contribute to diabetic complications, including bone defects. In the present study, the effect of sciadopitysin on MG-induced cytotoxicity was investigated using osteoblastic MC3T3-E1 cells. Pretreatment of MC3T3-E1 cells with sciadopitysin prevented the MG-induced cell death and protein adducts formation. Sciadopitysin restored the MG-induced change in glyoxalase activity almost to the control level and increased glutathione levels. In addition, sciadopitysin decreased MG-induced formation of intracellular reactive oxygen species (ROS), mitochondrial superoxide, and cardiolipin peroxidation. These findings suggest that sciadopitysin provides a protective action against MG-induced glycation by increasing MG detoxification system and by reducing oxidative stress. Pretreatment with sciadopitysin prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential (MMP) dissipation and adenosine triphosphate (ATP) loss. The nitric oxide (NO) level was decreased by MG treatment, but it was significantly increased by sciadopitysin, suggesting that sciadopitysin may induce NO-dependent mitochondrial biogenesis. Furthermore, sciadopitysin treatment increased the levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM). These findings indicate that sciadopitysin might exert its therapeutic effects via upregulation of mitochondrial biogenesis. Therefore, sciadopitysin may prevent the development of diabetic osteopathy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP521346	Sciadopitysin		521-34-6	Price

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