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20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol Suppresses UV-Induced MMP-1 Expression Through AMPK-mediated mTOR Inhibition as a Downstream of the PKA-LKB1 Pathway

20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol Suppresses UV-Induced MMP-1 Expression Through AMPK-mediated mTOR Inhibition as a Downstream of the PKA-LKB1 Pathway

Dong Joo Shin, Jong-Eun Kim, Tae-Gyu Lim, Eun Hee Jeong, Gaeun Park, Nam Joo Kang, Jun-Seong Park, Myeong-Hun Yeom, Deok Kun Oh, Ann M Bode, Zigang Dong, Hyong Joo Lee, Ki Won Lee

J Cell Biochem. 2014 Oct;115(10):1702-11.

PMID: 24821673

Abstract:

Various health effects have been attributed to the ginsenoside metabolite 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD); however, its effect on ultraviolet (UV)-induced matrix metalloproteinase (MMP)-1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV-induced MMP-1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV-induced MMP-1 expression in HDFs and suppressed the UV-induced phosphorylation of mammalian target of rapamycin (mTOR) and p70(S6K) without inhibiting the activity of phosphatidylinositol 3-kinase and Akt, which are well-known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5'-monophosphate (AICAR), an activator of AMPK, augmented UV-induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP-1 expression. AICAR also decreased the phosphorylation of mTOR and p70(S6K). However, compound C, an antagonist of AMPK, increased MMP-1 expression. In HDF cells with AMPK knock-down using shRNA, MMP-1 expression was increased. These results indicate that AMPK activation plays a key role in MMP-1 suppression. Additionally, the cAMP-dependent protein kinase (PKA) inhibitor, H-89, antagonized GPD-mediated MMP-1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV-induced MMP-1 expression is due to the activation of AMPK as a downstream of the PKA-LKB1 pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP3031945	5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate		3031-94-5	Price

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