TY - JOUR
T1 - Dimethyl α-Ketoglutarate Promotes the Synthesis of Collagen and Inhibits Metalloproteinases in HaCaT Cells
AU - Yu, Bo Yeong
AU - Eom, Da Hae
AU - Kim, Hyun Woo
AU - Jeong, Yong Joo
AU - Keum, Young Sam
N1 - Publisher Copyright:
© 2024 The Korean Society of Applied Pharmacology.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - 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 deriva-tive 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.
AB - 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 deriva-tive 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.
KW - 4-Hydroxyproline
KW - Activator protein-1 (AP-1)
KW - Dimethyl α-ketoglutarate (DMK)
KW - Interleukin-1α (IL-1α)
KW - Matrix metalloproteinases (MMPs)
UR - http://www.scopus.com/inward/record.url?scp=85186444071&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2023.131
DO - 10.4062/biomolther.2023.131
M3 - Article
AN - SCOPUS:85186444071
SN - 1976-9148
VL - 32
SP - 240
EP - 248
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 2
ER -