PMID- 15120611
OWN - NLM
STAT- MEDLINE
DCOM- 20040625
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 318
IP  - 2
DP  - 2004 May 28
TI  - 5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide-induced 
      TNF-alpha production through inhibition of phosphatidylinositol 3-kinase/Akt 
      activation in RAW 264.7 murine macrophages.
PG  - 372-80
AB  - 5-Aminoimidazole-4-carboxamide riboside (AICAR) is an adenosine analog and a 
      widely used activator of AMP-activated protein kinase (AMPK). We examined the 
      effect of AICAR on LPS-induced TNF-alpha production in RAW 264.7 and peritoneal 
      macrophages and its molecular mechanism in RAW 264.7 macrophages. Treatment with 
      AICAR inhibited LPS-induced increases in TNF-alpha mRNA and protein levels in 
      these cells. AICAR or LPS did not alter the AMPK activity as well as the 
      phosphorylations of AMPK alpha (Thr172) and ACC (Ser79). Moreover, an adenosine 
      kinase inhibitor 5'-iodotubercidin enhanced the suppressive effect of AICAR on 
      TNF-alpha levels. These results suggest that the effect of AICAR on TNF-alpha 
      suppression in RAW 264.7 cells is independent of AMPK activation. In addition, an 
      adenosine receptor antagonist 8-SPT had no effect on AICAR-induced suppression of 
      TNF-alpha levels. Finally, we observed that AICAR inhibited LPS-induced 
      activation of PI 3-kinase and Akt, whereas it had no effect on the activation of 
      p38 and ERK1/2. Taken together, these results suggest that the anti-inflammatory 
      action of AICAR in RAW 264.7 macrophages is independent of AMPK activation and is 
      associated with inhibition of LPS-induced activation of PI 3-kinase/Akt pathway.
FAU - Jhun, Bong Sook
AU  - Jhun BS
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee 
      University, Seoul 130-701, Republic of Korea.
FAU - Jin, Quanri
AU  - Jin Q
FAU - Oh, Young Taek
AU  - Oh YT
FAU - Kim, Sung Soo
AU  - Kim SS
FAU - Kong, Yoon
AU  - Kong Y
FAU - Cho, Yong Ho
AU  - Cho YH
FAU - Ha, Joohun
AU  - Ha J
FAU - Baik, Hyung Hwan
AU  - Baik HH
FAU - Kang, Insug
AU  - Kang I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Nucleoside Transport Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Purinergic P1 Receptor Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.1.20 (Adenosine Kinase)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Adenosine/antagonists & inhibitors
MH  - Adenosine Kinase/antagonists & inhibitors
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/*pharmacology
MH  - Animals
MH  - Cell Line
MH  - Enzyme Inhibitors/pharmacology
MH  - Lipopolysaccharides/*antagonists & inhibitors/pharmacology
MH  - Macrophages/drug effects/enzymology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Multienzyme Complexes/metabolism
MH  - Nucleoside Transport Proteins/antagonists & inhibitors
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/*antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Purinergic P1 Receptor Antagonists
MH  - RNA, Messenger/antagonists & inhibitors/biosynthesis
MH  - Rats
MH  - Ribonucleotides/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/biosynthesis
EDAT- 2004/05/04 05:00
MHDA- 2004/06/26 05:00
CRDT- 2004/05/04 05:00
PHST- 2004/01/19 00:00 [received]
PHST- 2004/05/04 05:00 [pubmed]
PHST- 2004/06/26 05:00 [medline]
PHST- 2004/05/04 05:00 [entrez]
AID - S0006291X04007600 [pii]
AID - 10.1016/j.bbrc.2004.04.035 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 May 28;318(2):372-80. doi: 
      10.1016/j.bbrc.2004.04.035.