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Iranian Journal of Basic Medical Sciences، جلد ۱۹، شماره ۱۲، صفحات ۱۳۰۸-۱۳۱۷
عنوان فارسی
چکیده فارسی مقاله
کلیدواژه‌های فارسی مقاله
عنوان انگلیسی Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue
چکیده انگلیسی مقاله 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.
کلیدواژه‌های انگلیسی مقاله ACC, A-769662, AMPK, Compound-C Lipopolysaccharide, TLR-4
نویسندگان مقاله مریم رامش راد | maryam rameshrad
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

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)

نسرین مالکی دیزجی | nasrin maleki dizaji
department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)

حمید ثریا | hamid soraya
department of pharmacology, faculty of pharmacy, urmia university of medical sciences, urmia, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی ارومیه (Urmia university of medical sciences)

نگیسا سید توتونچی | negisa seyed toutounchi
student research committee, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)

ابوالفضل برزگری | abolfazl barzegari
research center for pharmaceutical nanotechnology, tabriz university of medical sciences, tabriz, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)

علیرضا گرجانی | alireza garjani
department of pharmacology and toxicology, faculty of pharmacy, tabriz university of medical sciences, tabriz, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تبریز (Tabriz university of medical sciences)

نشانی اینترنتی http://ijbms.mums.ac.ir/article_7917.html
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زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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