Dimethyl α-Ketoglutarate Promotes the Synthesis of Collagen and Inhibits Metalloproteinases in HaCaT Cells
10.4062/biomolther.2023.131
- Author:
Bo-Yeong YU
1
;
Da-Hae EOM
;
Hyun Woo KIM
;
Yong-Joo JEONG
;
Young-Sam KEUM
Author Information
1. College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, Goyang 10326, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2024;32(2):240-248
- CountryRepublic of Korea
- Language:EN
-
Abstract:
We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and downregulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.
