Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Dimethyl α-Ketoglutarate Promotes the Synthesis of Collagen and Inhibits Metalloproteinases in HaCaT Cells

  • Bo-Yeong Yu (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University) ;
  • Da-Hae Eom (Panacea Company) ;
  • Hyun Woo Kim (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University) ;
  • Yong-Joo Jeong (School of Applied Chemistry, Kookmin University) ;
  • Young-Sam Keum (College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University)
  • Received : 2023.07.19
  • Accepted : 2023.08.14
  • Published : 2024.03.01
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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 down-regulated 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.

Keywords

Acknowledgement

This research was supported by the National Research Industrial Cluster Competitiveness Reinforcement project funded by the Korea Industrial Complex Corporation (KICOX, IRIC2210).

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