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Article

A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats

  • Authors:
    • Maryam Rameshrad
    • Hamid Soraya
    • Nasrin Maleki‑Dizaji
    • Haleh Vaez
    • Alireza Garjani
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan 51656‑65811, Iran, Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, West Azerbaijan 54147‑83734, Iran, Cardiovascular Research Centre, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan 51656‑65811, Iran
  • Pages: 2843-2849
    |
    Published online on: January 28, 2016
       https://doi.org/10.3892/mmr.2016.4821
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Abstract

Activation of AMP‑activated protein kinase (AMPK) has been indicated to produce an anti‑inflammatory effect through the suppression of toll‑like receptor (TLR) activity. In the present study, the investigation was designed to identify the effect of A‑769662, a direct activator of AMPK on lipopolysaccharide (LPS)‑induced acute lung and heart inflammation in rats. To induce inflammation, an intraperitoneal injection of LPS (0.5 mg/kg) was administered to Wistar rats. The inflammatory parameters and AMPK phosphorylation were then measured 9 h later. For the treatment group, A‑769662 (10 mg/kg) was administrated intraperitoneally immediately prior to LPS injection. The results demonstrated that A‑769662 attenuated the LPS‑induced acute inflammation in the heart and lung tissue, as indicated by the significant reduction in myeloperoxidase activity (P<0.001) and inhibition of tissue damage. This was associated with a significant reduction in tumor necrosis factor‑α serum levels (P<0.01) and peripheral neutrophils (P<0.001). Furthermore, A‑769662 enhanced AMPK phosphorylation and downregulated the expression of MyD88, a TLR adaptor protein, in the heart tissue. Despite the anti‑inflammatory effect of A‑769662 on LPS‑induced inflammation in the lung tissue, the drug produced no effect on the MyD88 expression levels or AMPK phosphorylation in the tissue. The results of the present study suggested that the administration of A‑769662 results in an anti‑inflammatory effect in the LPS‑induced model of inflammation in rats. The anti‑inflammatory activity was demonstrated in the heart and lung tissues and the effect on the cardiac tissue was indicated to be a result of AMPK activation, involving the suppression of TLRs.
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1 

Akira S and Takeda K: Toll-like receptor signalling. Nat Rev Immunol. 4:499–511. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Takeda K: Evolution and integration of innate immune recognition systems: The Toll-like receptors. J Endotoxin Res. 11:51–55. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Beutler B: Inferences, questions and possibilities in Toll-like receptor signalling. Nature. 430:257–263. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Cristofaro P and Opal SM: Role of Toll-like receptors in infection and immunity: Clinical implications. Drugs. 66:15–29. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Reitsma PH, Branger J, Van Den Blink B, Weijer S, Van Der Poll T and Meijers JC: Procoagulant protein levels are differentially increased during human endotoxemia. J Thromb Haemost. 1:1019–1023. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Ramana KV, Willis MS, White MD, Horton JW, DiMaio JM, Srivastava D, Bhatnagar A and Srivastava SK: Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition. Circulation. 114:1838–1846. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Jardin F, Brun-Ney D, Auvert B, Beauchet A and Bourdarias JP: Sepsis-related cardiogenic shock. Crit Care Med. 18:1055–1060. 1990. View Article : Google Scholar : PubMed/NCBI

8 

Connor AJ, Chen LC, Joseph LB, Laskin JD and Laskin DL: Distinct responses of lung and liver macrophages to acute endotoxemia: Role of toll-like receptor 4. Exp Mol Pathol. 94:216–227. 2013. View Article : Google Scholar :

9 

Soraya H, Farajnia S, Khani S, Rameshrad M, Khorrami A, Banani A, Maleki-Dizaji N and Garjani A: Short-term treatment with metformin suppresses toll like receptors (TLRs) activity in isoproterenol-induced myocardial infarction in rat: Are AMPK and TLRs connected? Int Immunopharmacol. 14:785–791. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Soraya H, Clanachan AS, Rameshrad M, Maleki-Dizaji N, Ghazi-Khansari M and Garjani A: Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction. Eur J Pharmacol. 737:77–84. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Bai A, Ma AG, Yong M, Weiss CR, Ma Y, Guan Q, Bernstein CN and Peng Z: AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis. Biochem Pharmacol. 80:1708–1717. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Nath N, Giri S, Prasad R, Salem ML, Singh AK and Singh I: 5-aminoimidazole-4-carboxamide ribonucleoside: A novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis. J Immunol. 175:566–574. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Zhao X, Zmijewski JW, Lorne E, Liu G, Park YJ, Tsuruta Y and Abraham E: Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 295:L497–L504. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Shirwany NA and Zou MH: AMPK in cardiovascular health and disease. Acta Pharmacol Sin. 31:1075–1084. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Young LH, Li J, Baron SJ and Russell RR: AMP-activated protein kinase: A key stress signaling pathway in the heart. Trends Cardiovasc Med. 15:110–118. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Dyck JR and Lopaschuk GD: AMPK alterations in cardiac physiology and pathology: Enemy or ally? J Physiol. 574:95–112. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Hardie DG, Carling D and Gamblin SJ: AMP-activated protein kinase: Also regulated by ADP? Trends Biochem Sci. 36:470–477. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Hardie DG: Minireview: The AMP-activated protein kinase cascade: The key sensor of cellular energy status. Endocrinology. 144:5179–5183. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Kemp BE: Bateman domains and adenosine derivatives form a binding contract. J Clin Invest. 113:182–184. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Kim AS, Miller EJ, Wright TM, Li J, Qi D, Atsina K, Zaha V, Sakamoto K and Young LH: A small molecule AMPK activator protects the heart against ischemia-reperfusion injury. J Mol Cell Cardiol. 51:24–32. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, et al: Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 3:403–416. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, Viollet B, Hardie DG and Sakamoto K: Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 282:32549–32560. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Zhao X, Petursson F, Viollet B, Lotz M, Terkeltaub R and Liu-Bryan R: Peroxisome proliferator-activated receptor γ coactivator 1α and FoxO3A mediate chondroprotection by AMP-activated protein kinase. Arthritis Rheumatol. 66:3073–3082. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Petursson F, Husa M, June R, Lotz M, Terkeltaub R and Liu-Bryan R: Linked decreases in liver kinase B1 and AMP-activated protein kinase activity modulate matrix catabolic responses to biomechanical injury in chondrocytes. Arthritis Res Ther. 15:R772013. View Article : Google Scholar : PubMed/NCBI

25 

Meng X, Ao L, Meldrum DR, Cain BS, Shames BD, Selzman CH, Banerjee A and Harken AH: TNF-alpha and myocardial depression in endotoxemic rats: Temporal discordance of an obligatory relationship. Am J Physiol. 275:R502–R508. 1998.PubMed/NCBI

26 

Copeland S, Warren HS, Lowry SF, Calvano SE and Remick D; Inflammation and the Host Response to Injury Investigators: Acute inflammatory response to endotoxin in mice and humans. Clin Diagn Lab Immunol. 12:60–67. 2005.PubMed/NCBI

27 

Turyn D, Dominici FP, Sotelo AI and Bartke A: Specific interactions of growth hormone (GH) with GH-receptors and GH-binding proteins in vivo in genetically GH-deficient Ames dwarf mice. Growth Horm IGF Res. 8:389–396. 1998. View Article : Google Scholar

28 

Lu YC, Yeh WC and Ohashi PS: LPS/TLR4 signal transduction pathway. Cytokine. 42:145–151. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Lefort J, Singer M, Leduc D, Renesto P, Nahori MA, Huerre M, Créminon C, Chignard M and Vargaftig BB: Systemic administration of endotoxin induces bronchopulmonary hyperreactivity dissociated from TNF-alpha formation and neutrophil sequestration into the murine lungs. J Immunol. 161:474–480. 1998.PubMed/NCBI

30 

Kim M and Tian R: Targeting AMPK for cardiac protection: Opportunities and challenges. J Mol Cell Cardiol. 51:548–553. 2011. View Article : Google Scholar :

31 

Timmermans AD, Balteau M, Gélinas R, Renguet E, Ginion A, de Meester C, Sakamoto K, Balligand JL, Bontemps F, Vanoverschelde JL, et al: A-769662 potentiates the effect of other AMP-activated protein kinase activators on cardiac glucose uptake. Am J Physiol Heart Circ Physiol. 306:H1619–H1630. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Salminen A, Hyttinen JM and Kaarniranta K: AMP-activated protein kinase inhibits NF-κB signaling and inflammation: Impact on healthspan and lifespan. J Mol Med Berl. 89:667–676. 2011. View Article : Google Scholar

33 

Myerburg MM, King JD Jr, Oyster NM, Fitch AC, Magill A, Baty CJ, Watkins SC, Kolls JK, Pilewski JM and Hallows KR: AMPK agonists ameliorate sodium and fluid transport and inflammation in cystic fibrosis airway epithelial cells. Am J Respir Cell Mol Biol. 42:676–684. 2010. View Article : Google Scholar :

34 

Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, et al: Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 331:456–461. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Hattori Y, Nakano Y, Hattori S, Tomizawa A, Inukai K and Kasai K: High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-kappaB activation in vascular endothelial cells. FEBS Lett. 582:1719–1724. 2008. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Rameshrad M, Soraya H, Maleki‑Dizaji N, Vaez H and Garjani A: A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats. Mol Med Rep 13: 2843-2849, 2016.
APA
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., & Garjani, A. (2016). A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats. Molecular Medicine Reports, 13, 2843-2849. https://doi.org/10.3892/mmr.2016.4821
MLA
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., Garjani, A."A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats". Molecular Medicine Reports 13.3 (2016): 2843-2849.
Chicago
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., Garjani, A."A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats". Molecular Medicine Reports 13, no. 3 (2016): 2843-2849. https://doi.org/10.3892/mmr.2016.4821
Copy and paste a formatted citation
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Spandidos Publications style
Rameshrad M, Soraya H, Maleki‑Dizaji N, Vaez H and Garjani A: A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats. Mol Med Rep 13: 2843-2849, 2016.
APA
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., & Garjani, A. (2016). A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats. Molecular Medicine Reports, 13, 2843-2849. https://doi.org/10.3892/mmr.2016.4821
MLA
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., Garjani, A."A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats". Molecular Medicine Reports 13.3 (2016): 2843-2849.
Chicago
Rameshrad, M., Soraya, H., Maleki‑Dizaji, N., Vaez, H., Garjani, A."A‑769662, a direct AMPK activator, attenuates lipopolysaccharide‑induced acute heart and lung inflammation in rats". Molecular Medicine Reports 13, no. 3 (2016): 2843-2849. https://doi.org/10.3892/mmr.2016.4821
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