Alpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts, and decreases UVB-induced wrinkle formation following topical application on the dorsal skin of hairless mice.
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 alpha-ketoglutarate remain as yet unreported. To investigate the effects of alpha-ketoglutarate on procollagen production and wrinkle formation, we conducted experiments in cultured human dermal fibroblasts and UVB-irradiated hairless mice. Based on ELISA measurements, alpha-ketoglutarate (10 microM) stimulated procollagen production in fibroblasts by 25.6+/-4.6% compared to vehicle (dH(2)O)-treated control cells. Also, we demonstrated that alpha-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 alpha-ketoglutarate in fibroblasts. To determine the effect of topically applied alpha-ketoglutarate on wrinkle formation, alpha-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 alpha-ketoglutarate decreased wrinkle formation upon long-term topical application. These results suggest that alpha-ketoglutarate diminishes UVB-induced wrinkle formation by increasing collagen production, through a pathway that involves prolidase activation. Therefore, application of alpha-ketoglutarate may represent an effective anti-wrinkle agent for the cosmetic field.
AmorePacific Corporation R&D Center, 314-1 Bora-Dong, Giheung-gu, Yongin-si, Kyeonggi-do 446-729, Korea.
Eui Dong
ED
Son
Gyu Ho
GH
Choi
Hyaekyoung
H
Kim
Byoungseok
B
Lee
Ih Seoup
IS
Chang
Jae Sung
JS
Hwang
D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007656:Ketoglutaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D011347:Procollagen / Q000096:biosynthesis*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects*; D013268:Stimulation, Chemical; D013778:Tetrazolium Salts; D013844:Thiazoles; D014466:Ultraviolet Rays
D024042:Collagen Type I; D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D011347:Procollagen; D013778:Tetrazolium Salts; D013844:Thiazoles; C506055:benzyloxycarbonylproline; D011392:Proline; D004150:Dipeptidases; C022449:proline dipeptidase; C022616:thiazolyl blue