Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

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RAMESHRAD MARYAM; MALEKI DIZAJI NASRIN; SORAYA HAMID; SEYED TOUTOUNCHI NEGISA; BARZEGARI ABOLFAZL; GARJANI ALIREZA

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Journal: Iranian Journal of Basic Medical Sciences Year:2016 | Volume:19 | Issue:12 Page(s): 1308-1317

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Title

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

Author(s)

Keywords

ACC

A-769662

AMPK

Compound-C

Lipopolysaccharide TLR-4

Abstract

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.

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APA: Copy

RAMESHRAD, MARYAM, MALEKI DIZAJI, NASRIN, SORAYA, HAMID, SEYED TOUTOUNCHI, NEGISA, BARZEGARI, ABOLFAZL, & GARJANI, ALIREZA. (2016). Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 19(12), 1308-1317. SID. https://sid.ir/paper/725249/en

Vancouver: Copy

RAMESHRAD MARYAM, MALEKI DIZAJI NASRIN, SORAYA HAMID, SEYED TOUTOUNCHI NEGISA, BARZEGARI ABOLFAZL, GARJANI ALIREZA. Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2016;19(12):1308-1317. Available from: https://sid.ir/paper/725249/en

IEEE: Copy

MARYAM RAMESHRAD, NASRIN MALEKI DIZAJI, HAMID SORAYA, NEGISA SEYED TOUTOUNCHI, ABOLFAZL BARZEGARI, and ALIREZA GARJANI, “Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 19, no. 12, pp. 1308–1317, 2016, [Online]. Available: https://sid.ir/paper/725249/en

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