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AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H2S, NO, and CO.
Nitric Oxide. 2018 08 01; 78:60-71.NO

Abstract

Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.

Authors+Show Affiliations

Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil.Departments of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil.Postgraduate Program in Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University Ceará, Fortaleza, Ceará, Brazil.Postgraduate Program in Morphofunctional Sciences, Department of Morphology, Faculty of Medicine, Federal University Ceará, Fortaleza, Ceará, Brazil.Departments of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil.Departments of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil.Laboratory of Pharmacology of Inflammation and Gastrointestinal Disorders (LAFIDG), Federal University of Piauí, Parnaíba, Piauí, Brazil. Electronic address: jandvenes@ufpi.edu.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29857061

Citation

de Araújo, Simone, et al. "AMPK Activation Promotes Gastroprotection Through Mutual Interaction With the Gaseous Mediators H2S, NO, and CO." Nitric Oxide : Biology and Chemistry, vol. 78, 2018, pp. 60-71.
de Araújo S, Oliveira AP, Sousa FBM, et al. AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H2S, NO, and CO. Nitric Oxide. 2018;78:60-71.
de Araújo, S., Oliveira, A. P., Sousa, F. B. M., Souza, L. K. M., Pacheco, G., Filgueiras, M. C., Nicolau, L. A. D., Brito, G. A. C., Cerqueira, G. S., Silva, R. O., Souza, M. H. L. P., & Medeiros, J. V. R. (2018). AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H2S, NO, and CO. Nitric Oxide : Biology and Chemistry, 78, 60-71. https://doi.org/10.1016/j.niox.2018.05.008
de Araújo S, et al. AMPK Activation Promotes Gastroprotection Through Mutual Interaction With the Gaseous Mediators H2S, NO, and CO. Nitric Oxide. 2018 08 1;78:60-71. PubMed PMID: 29857061.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H2S, NO, and CO. AU - de Araújo,Simone, AU - Oliveira,Ana P, AU - Sousa,Francisca B M, AU - Souza,Luan K M, AU - Pacheco,Gabriella, AU - Filgueiras,Marcelo C, AU - Nicolau,Lucas A D, AU - Brito,Gerly Anne C, AU - Cerqueira,Gilberto S, AU - Silva,Renan O, AU - Souza,Marcellus H L P, AU - Medeiros,Jand Venes R, Y1 - 2018/05/30/ PY - 2018/02/19/received PY - 2018/04/25/revised PY - 2018/05/29/accepted PY - 2018/6/2/pubmed PY - 2019/9/4/medline PY - 2018/6/2/entrez KW - AMPK KW - Carbon monoxide KW - Ethanol KW - Hydrogen sulfide KW - Nitric oxide SP - 60 EP - 71 JF - Nitric oxide : biology and chemistry JO - Nitric Oxide VL - 78 N2 - Activation of 5' adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3-/NO2-), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3-/NO2- levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3-/NO2- levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process. SN - 1089-8611 UR - https://www.unboundmedicine.com/medline/citation/29857061/AMPK_activation_promotes_gastroprotection_through_mutual_interaction_with_the_gaseous_mediators_H2S_NO_and_CO_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089-8603(18)30050-8 DB - PRIME DP - Unbound Medicine ER -