Dimethyl α-Ketoglutarate Promotes the Synthesis of Collagen and Inhibits Metalloproteinases in HaCaT Cells

• Published in: Biomolecules & therapeutics Vol. 32; no. 2; pp. 240 - 248
• Main Authors: Yu, Bo-Yeong, Eom, Da-Hae, Kim, Hyun Woo, Jeong, Yong-Joo, Keum, Young-Sam
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.03.2024; 한국응용약물학회
• Subjects: Original; 약학; 4-Hydroxyproline; Matrix metalloproteinases (MMPs); Activator protein-1 (AP-1); Interleukin-1α (IL-1α); Dimethyl α-ketoglutarate (DMK)
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2023.131

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.