著者

Eui Dong Son Gyu Ho Choi Hyaekyoung Kim Byoungseok Lee Ih Seoup Chang Jae Sung Hwang

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.8, pp.1395-1399, 2007-08-01 (Released:2007-08-01)

参考文献数

24

被引用文献数

26 37

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Alpha-ketoglutarate is a key intermediate in the Krebs cycle, and a rate-limiting cofactor of prolyl-4-hydroxylase. It also has a potent effect on increasing the proline pool during collagen production, but the details underlying the boosting effect on collagen production by α-ketoglutarate remain as yet unreported. To investigate the effects of α-ketoglutarate on procollagen production and wrinkle formation, we conducted experiments in cultured human dermal fibroblasts and UVB-irradiated hairless mice. Based on ELISA measurements, α-ketoglutarate (10 μM) stimulated procollagen production in fibroblasts by 25.6±4.6% compared to vehicle (dH2O)-treated control cells. Also, we demonstrated that α-ketoglutarate increased activities of prolidase, which is known to play an important role in collagen metabolism, in fibroblasts and N-benzyloxycarbonyl-L-proline (Cbz-Pro), prolidase inhibitor, inhibited procollagen synthesis by α-ketoglutarate in fibroblasts. To determine the effect of topically applied α-ketoglutarate on wrinkle formation, α-ketoglutarate (1%) and vehicle (70% propylene glycol, 30% ethanol) were applied on the dorsal skin of UVB-induced hairless mice for twelve weeks. We found that α-ketoglutarate decreased wrinkle formation upon long-term topical application. These results suggest that α-ketoglutarate diminishes UVB-induced wrinkle formation by increasing collagen production, through a pathway that involves prolidase activation. Therefore, application of α-ketoglutarate may represent an effective anti-wrinkle agent for the cosmetic field.