title: Effect of A-769662, a direct AMPK activator, onTlr-4expression and activity in mice heart tissue.
abstract: OBJECTIVE
  TLR-4 activates a number of inflammatory signaling pathways. Also, AMPK could be involved in anti-inflammatory signaling. The aim of this study was to identify whether stimulation of AMPK could inhibit LPS-inducedTlr-4 gene expression in mice hearts.
  
  
  METHODS
  Heart AMPK activity and/orTlr-4 expression was stimulated in different mice groups, using respectively IP injection of A-769662 (10 mg/kg) and LPS (2 mg/kg) or a combination of both agents. Moreover, compound-C (20 mg/kg), as an AMPK antagonist, was intraperitoneally co-administrated with both A-769662 and LPS in another group to investigate the role of AMPK activity onTlr-4 regulation. After 8 hr, in addition to peripheral neutrophil cell count, myocardial p-AMPK, p-ACC as well as MyD88 protein contents andTlr-4 expression was assessed by Western blotting and real-time qRT-PCR, respectively. TNF-α and IL-6 expression levels were also determined by ELISA.
  
  
  RESULTS
  LPS induced heartTlr-4 expression (P<0.001) associating with an increase in the myocardial MyD88 protein content (P<0.001), elevation of heart TNF-α (P<0.01) and IL-6 (P<0.05) concentrations, and rise in the peripheral neutrophil cell count (P<0.001). Administration of A-769662 decreased LPS-inducedTlr-4 expression (P<0.01) and alleviated peripheral neutrophil cell count (P<0.01). The inhibitory effect of A-769662 on LPS-inducedTlr-4 expression was reversed by antagonizing AMPK with compound-C (P<0.001) which reduced p-AMPK (P<0.05) and p-ACC (P<0.01) myocardial protein contents in the LPS+A-769662 group.
  
  
  CONCLUSIONS
  This study demonstrated that activation of AMPK, by A-769662 agent, could inhibitTlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rameshrad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Soraya
authors.affiliation: Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Negisa Seyed
authors.initials: NS
authors.lastname: Toutounchi
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Barzegari
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Garjani
keywords: A-769662; ACC; AMPK; Compound-C Lipopolysaccharide; TLR-4