AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H 2 S, NO, and CO

Araújo, Simone de; Oliveira, Ana Patrícia de; Sousa, Francisca Beatriz M.; Souza, Luan Kelves Miranda de; Pacheco, Gabriella; Filgueiras, Marcelo Carvalho; Nicolau, Lucas A.D.; Brito, Gerly A.C.; Cerqueira, Gilberto Santos; Silva, Renan O.; Souza, Marcellus H.; Medeiros, Jand Venes R.

doi:10.1016/j.niox.2018.05.008

Cited by 20 publications

(12 citation statements)

References 57 publications

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“…Previously, we have demonstrated that locally increased bioavailability of CO prevented gastric mucosa against ethanol-induced necrotic damage and that this effect was accompanied by the enhancement in GBF [ 12 ]. This observation has been confirmed also in other studies showing that CO prevents gastric mucosa against necrotic damage by its interaction with 5’ adenosine monophosphate-activated protein kinase [ 14 ]. However, the interaction of neuromediator released from afferent C fiber endings with gaseous molecule CO in the pathogenesis of ethanol-induced gastric damage still remains unexplored.…”

Section: Discussionsupporting

confidence: 83%

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Magierowska

Wójcik

Chmura

et al. 2018

IJMS

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Carbon monoxide (CO) has been reported to contribute to the maintenance of gastric mucosal integrity, gastroprotection, and ulcer healing. However, involvement of transient receptor potential vanilloid receptor type 1 (TRPV1) located on afferent sensory fibers endings and sensory neuropeptide calcitonin gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol-induced gastric damage has not been explored. Male Wistar rats with and without denervation of afferent sensory neurons induced by capsaicin (total dose 125 mg/kg within 3 days) were pretreated with vehicle, CO donor tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered alone or with CGRP-α (10 μg/kg i.p.) or TRPV1 antagonist capsazepine (5 mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75% ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed planimetrically and by laser flowmetry, respectively. Microscopic evaluation of ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-α, CGRP-β, inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS, cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was determined by real-time PCR or Western blot, respectively. Pretreatment with CORM-2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in capsaicin-denervated animals failed to affect these beneficial effects of CO donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level for HMOX-1 and CGRP-α. In capsaicin-denervated rats, CORM-2 increased eNOS mRNA fold change and TRPV1 protein expression while capsaicin denervation itself decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO prevents gastric mucosa from ethanol-induced lesions due to activation of TRPV1/CGRP-α system and accompanying increase in gastric microcirculation but independently on afferent sensory nerve activity despite the stimulation of TRPV1 protein and CGRP-α mRNA expression.

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Section: Discussionsupporting

confidence: 83%

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Magierowska

Wójcik

Chmura

et al. 2018

IJMS

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“…Similarly, CORM-2 dose-dependently elevated HCO 3 secretion acting as the stimulant of endogenous PGs biosynthesis [62]. In another study, de Araujo et al proposed that adenosine monophosphate-activated protein kinase (AMPK) plays an important role as a regulator of cellular energy and metabolism, and could be the common target for all above mentioned gaseous mediators [65]. Indeed, AMPK inducers can actually exert a beneficial effects within the GI tract, e.g., metformin has been shown to suppress esophageal squamous cell carcinoma (ESCC) [66].…”

Section: Parallelisms and Discrepancies In Co And H 2 S Effects And Tmentioning

confidence: 99%

“…Interestingly, the γ-subunit of AMPK contains four CBS domains located close to the N-terminus of this subunit, operating in pairs known as Bateman's domain [67]. The administration of H 2 S, CO and NO donors increased p-AMPK expression and protected gastric mucosa of mice against ethanol-induced lesions [65]. On the other hand, it has been also indicated that AMPK stimulates HMOX-1 gene expression within human vascular cells and rat arteries via modulation of Nrf2/ARE pathway [6].…”

Section: Parallelisms and Discrepancies In Co And H 2 S Effects And Tmentioning

confidence: 99%

Synergisms, Discrepancies and Interactions between Hydrogen Sulfide and Carbon Monoxide in the Gastrointestinal and Digestive System Physiology, Pathophysiology and Pharmacology

2020

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Endogenous gas transmitters, hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) are important signaling molecules known to exert multiple biological functions. In recent years, the role of H2S, CO and NO in regulation of cardiovascular, neuronal and digestive systems physiology and pathophysiology has been emphasized. Possible link between these gaseous mediators and multiple diseases as well as potential therapeutic applications has attracted great attention from biomedical scientists working in many fields of biomedicine. Thus, various pharmacological tools with ability to release CO or H2S were developed and implemented in experimental animal in vivo and in vitro models of many disorders and preliminary human studies. This review was designed to review signaling functions, similarities, dissimilarities and a possible cross-talk between H2S and CO produced endogenously or released from chemical donors, with special emphasis on gastrointestinal digestive system pathologies prevention and treatment.

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“…( Wallace, 2010 ). Furthermore, endogenous and exogenous H 2 S released from chemical donors have been implicated in the mechanism of maintenance of gastric mucosal homeostasis and to protect the gastric mucosa against lesions induced by NSAIDs and other noxious factors ( Lou et al, 2008 ; Cipriani et al, 2013 ; Magierowski et al, 2015 ; Magierowski et al, 2016 ; de Araújo et al, 2018 ; Magierowski et al, 2018 ). Such a protective effect of H 2 S has also been demonstrated in the intestinal mucosa of NSAID-treated rats, which seems to be particularly important due to the current need for an effective therapy against the adverse effects of NSAIDs affecting the intestine ( Wallace and Wang, 2015 ).…”

Section: Gaseous Mediators-releasing Nsaids and Gi Tractmentioning

confidence: 99%

Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology

et al. 2021

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Non-steroidal anti-inflammatory drugs (NSAIDs) represent one of the most widely used classes of drugs and play a pivotal role in the therapy of numerous inflammatory diseases. However, the adverse effects of these drugs, especially when applied chronically, frequently affect gastrointestinal (GI) tract, resulting in ulceration and bleeding, which constitutes a significant limitation in clinical practice. On the other hand, it has been recently discovered that gaseous mediators nitric oxide (NO), hydrogen sulfide (H2S) and carbon monoxide (CO) contribute to many physiological processes in the GI tract, including the maintenance of GI mucosal barrier integrity. Therefore, based on the possible therapeutic properties of NO, H2S and CO, a novel NSAIDs with ability to release one or more of those gaseous messengers have been synthesized. Until now, both preclinical and clinical studies have shown promising effects with respect to the anti-inflammatory potency as well as GI-safety of these novel NSAIDs. This review provides an overview of the gaseous mediators-based NSAIDs along with their mechanisms of action, with special emphasis on possible implications for GI mucosal defense mechanisms.

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AMPK activation promotes gastroprotection through mutual interaction with the gaseous mediators H 2 S, NO, and CO

Cited by 20 publications

References 57 publications

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions

Synergisms, Discrepancies and Interactions between Hydrogen Sulfide and Carbon Monoxide in the Gastrointestinal and Digestive System Physiology, Pathophysiology and Pharmacology

Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology

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