PMID- 24821673
OWN - NLM
STAT- MEDLINE
DCOM- 20150514
LR  - 20220331
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 115
IP  - 10
DP  - 2014 Oct
TI  - 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol suppresses UV-Induced MMP-1 
      expression through AMPK-mediated mTOR inhibition as a downstream of the PKA-LKB1 
      pathway.
PG  - 1702-11
LID - 10.1002/jcb.24833 [doi]
AB  - Various health effects have been attributed to the ginsenoside metabolite 
      20-O-beta-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-beta-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.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Shin, Dong Joo
AU  - Shin DJ
AD  - WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for 
      Food and Bioconvergence, Seoul National University, Seoul, 151-921, Republic of 
      Korea.
FAU - Kim, Jong-Eun
AU  - Kim JE
FAU - Lim, Tae-Gyu
AU  - Lim TG
FAU - Jeong, Eun Hee
AU  - Jeong EH
FAU - Park, Gaeun
AU  - Park G
FAU - Kang, Nam Joo
AU  - Kang NJ
FAU - Park, Jun-Seong
AU  - Park JS
FAU - Yeom, Myeong-Hun
AU  - Yeom MH
FAU - Oh, Deok Kun
AU  - Oh DK
FAU - Bode, Ann M
AU  - Bode AM
FAU - Dong, Zigang
AU  - Dong Z
FAU - Lee, Hyong Joo
AU  - Lee HJ
FAU - Lee, Ki Won
AU  - Lee KW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Ginsenosides)
RN  - 0 (Isoquinolines)
RN  - 0 (Oxazines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Ribonucleotides)
RN  - 0 (Sulfonamides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 92353-97-4 (oxadin)
RN  - A9RLM212CY (ginsenoside M1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (STK11 protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - AMP-Activated Protein Kinases/*biosynthesis/genetics
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Cell Line
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - Fibroblasts
MH  - Ginsenosides/*pharmacology
MH  - Humans
MH  - Isoquinolines/pharmacology
MH  - Matrix Metalloproteinase 1/*biosynthesis
MH  - Oxazines/pharmacology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Ribonucleotides/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors
MH  - Sulfonamides/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Ultraviolet Rays
OTO - NOTNLM
OT  - 20-O-beta-D-GLUCOPYRANOSYL-20(S)-PROTOPANAXADIOL
OT  - AMPK
OT  - GINSENOSIDES
OT  - MMP-1
OT  - SKIN AGING
OT  - UV
OT  - mTOR
EDAT- 2014/05/14 06:00
MHDA- 2015/05/15 06:00
CRDT- 2014/05/14 06:00
PHST- 2013/05/13 00:00 [received]
PHST- 2014/05/08 00:00 [accepted]
PHST- 2014/05/14 06:00 [entrez]
PHST- 2014/05/14 06:00 [pubmed]
PHST- 2015/05/15 06:00 [medline]
AID - 10.1002/jcb.24833 [doi]
PST - ppublish
SO  - J Cell Biochem. 2014 Oct;115(10):1702-11. doi: 10.1002/jcb.24833.