Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 7، دوره 19، شماره 12، اسفند 2016، صفحه 1308-1317 اصل مقاله (1.21 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2016.7917 | ||
| نویسندگان | ||
| Maryam Rameshrad1، 2؛ Nasrin Maleki-Dizaji1؛ Hamid Soraya3؛ Negisa Seyed Toutounchi2؛ Abolfazl Barzegari4؛ Alireza Garjani* 1 | ||
| 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 2Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| 3Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran | ||
| 4Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran | ||
| چکیده | ||
| Objective(s): 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-induced Tlr-4 gene expression in mice hearts. Materials and methods: Heart AMPK activity and/or Tlr-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 on Tlr-4 regulation. After 8 hr, in addition to peripheral neutrophil cell count, myocardial p-AMPK, p-ACC as well as MyD88 protein contents and Tlr-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 heart Tlr-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-induced Tlr-4 expression (P<0.01) and alleviated peripheral neutrophil cell count (P<0.01). The inhibitory effect of A-769662 on LPS-induced Tlr-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. Conclusion: This study demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. | ||
| کلیدواژهها | ||
| ACC؛ A-769662؛ AMPK؛ Compound-C Lipopolysaccharide؛ TLR-4 | ||
| مراجع | ||
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