Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression

Sebastián, Valentina P.; Salazar, Geraldyne A.; Coronado-Arrázola, Irenice; Schultz, Bárbara M.; Vallejos, Omar P.; Berkowitz, Loni; Álvarez-Lobos, Manuel; Riedel, Claudia A.; Kalergis, Alexis M.; Bueno, Susan M.

doi:10.3389/fimmu.2018.01956

Cited by 64 publications

(55 citation statements)

References 125 publications

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“…(3) PPIA, has been reported to be overexpressed in several types of human cancers including gastric cancer [51,55]. (4) HMOX1 is considered to be the main protein for cytoprotection against various cell stresses, and increased expression of this protein was observed in several types of cancers [56,57]. However, there are no differences in the levels of PPIA and HOMX1 between GC and controls in serum or in tissue in the present study.…”

Section: Discussioncontrasting

confidence: 52%

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

et al. 2019

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Background: Gastric cancer (GC) is the third leading cause of cancer death. Early detection is a key factor to reduce its mortality. Methods: We retrospectively collected pre-and postoperative serum samples as well as tumour tissues and adjacent normal tissues from 100 GC patients. Serum samples from non-cancerous patients were served as controls (n = 50). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure levels of over 300 proteins. Alteration of each protein was analysed by univariate analysis. Elastic-net logistic regression was performed to select serum proteins into the diagnostic model. Findings: We identified 19 serum proteins (CEACAM5, CA9, MSLN, CCL20, SCF, TGF-alpha, MMP-1, MMP-10, IGF-1, CDCP1, PPIA, DDAH-1, HMOX-1, FLI1, IL-7, ZBTB-17, APBB1IP, KAZALD-1, and ADAMTS-15) that together distinguish GC cases from controls with a diagnostic sensitivity of 93%, specificity of 100%, and area under receiver operating characteristic curve (AUC) of 0·99 (95% CI: 0·98-1). Moreover, the 19-serum protein signature provided an increased diagnostic capacity in patients at TNM I-II stage (sensitivity 89%, specificity 100%, AUC 0·99) and in patients with high microsatellite instability (MSI) (91%, 98%, and 0·99) compared to individual proteins. These promising results will inspire a large-scale independent cohort study to be pursued for validating the proposed protein signature. Interpretation: Based on targeted proteomics and elastic-net logistic regression, we identified a 19-serum protein signature which could contribute to clinical GC diagnosis, especially for patients at early stage and those with high MSI. Fund: This study was supported by a European H2020-Marie Skłodowska-Curie Innovative Training Networks grant (316,929, GastricGlycoExplorer). Funder had no influence on trial design, data evaluation, and interpretation.EBioMedicine 44 (2019) 322-333Abbreviations: ADAMTS-15, A disintegrin and metalloproteinase with thrombospondin motifs 15; APBB1IP, Amyloid beta A4 precursor protein-binding family B member 1-interacting protein; CA9, Carbonic anhydrase 9; CCL20, C-C motif chemokine 20; CDCP1, CUB domain-containing protein 1; CEACAM5, Carcinoembryonic antigen-related cell adhesion molecule 5; DDAH1, dimethylarginine dimethylaminohydrolase 1; FLI-1, Friend leukemia integration 1 transcription factor; GCNT1, beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-Nacetylglucosaminyltransferase; HMOX1, Heme oxygenase 1; IGF1, Insulin-like growth factor I; IL-7, Interleukin-7; KAZALD1, Kazal-type serine protease inhibitor domain containing protein 1; MSLN, Mesothelin; MMP-1, Matrix metalloproteinase-1; MMP-10, Matrix metalloproteinase-10; PPIA, Peptidyl-prolyl cis-trans isomerase A; SCF, Stem cell factor/KIT ligand; TGF alpha, Transforming growth factor alpha; ZBTB-17, Zinc finger and BTB domain-containing protein 17.

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Section: Discussioncontrasting

confidence: 52%

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

et al. 2019

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“…Similar to HSP70, HO-1 is the stress-inducible isoform of the three HO isoforms described to date, providing a critical protective mechanism in avian systems responsible for adaptation to oxidative, inflammatory and cytotoxic stress [136,137]. In most tissues HO-1 is expressed at a relatively low house-keeping level and it can be induced by various oxidative stress-related insults including haem, ultraviolet light, heavy metals, cytokines, hydrogen peroxide, nitric oxide (NO) and glutathione depletion [138,139]. The vital role of HO-1 in adaptation to stress has been shown in HO-1-deficient animal models characterised by atypical pro-inflammatory immune response with increased apoptosis [113].…”

Section: Heme Oxygenase-1mentioning

confidence: 99%

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

et al. 2019

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Poultry in commercial settings are exposed to a range of stressors. A growing body of information clearly indicates that excess ROS/RNS production and oxidative stress are major detrimental consequences of the most common commercial stressors in poultry production. During evolution, antioxidant defence systems were developed in poultry to survive in an oxygenated atmosphere. They include a complex network of internally synthesised (e.g., antioxidant enzymes, (glutathione) GSH, (coenzyme Q) CoQ) and externally supplied (vitamin E, carotenoids, etc.) antioxidants. In fact, all antioxidants in the body work cooperatively as a team to maintain optimal redox balance in the cell/body. This balance is a key element in providing the necessary conditions for cell signalling, a vital process for regulation of the expression of various genes, stress adaptation and homeostasis maintenance in the body. Since ROS/RNS are considered to be important signalling molecules, their concentration is strictly regulated by the antioxidant defence network in conjunction with various transcription factors and vitagenes. In fact, activation of vitagenes via such transcription factors as Nrf2 leads to an additional synthesis of an array of protective molecules which can deal with increased ROS/RNS production. Therefore, it is a challenging task to develop a system of optimal antioxidant supplementation to help growing/productive birds maintain effective antioxidant defences and redox balance in the body. On the one hand, antioxidants, such as vitamin E, or minerals (e.g., Se, Mn, Cu and Zn) are a compulsory part of the commercial pre-mixes for poultry, and, in most cases, are adequate to meet the physiological requirements in these elements. On the other hand, due to the aforementioned commercially relevant stressors, there is a need for additional support for the antioxidant system in poultry. This new direction in improving antioxidant defences for poultry in stress conditions is related to an opportunity to activate a range of vitagenes (via Nrf2-related mechanisms: superoxide dismutase, SOD; heme oxygenase-1, HO-1; GSH and thioredoxin, or other mechanisms: Heat shock protein (HSP)/heat shock factor (HSP), sirtuins, etc.) to maximise internal AO protection and redox balance maintenance. Therefore, the development of vitagene-regulating nutritional supplements is on the agenda of many commercial companies worldwide.

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“…Experiments carried out in mice showed that enteric microbiota have the ability to regulate the activity of intestinal macrophages essential in killing pathogenic bacteria such as Salmonella enterica. This bactericidal effect was associated with an induction of HMOX-1/CO pathway by microbiota [49,73]. Moreover, the gut microbiota can produce CO due to the presence of enzymes with similar functions as HMOX-1.…”

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

confidence: 96%

“…Moreover, the gut microbiota can produce CO due to the presence of enzymes with similar functions as HMOX-1. In addition, CO can directly interact with heme-containing groups in some intestinal bacteria [73]. Importantly, in patients with ulcerative colitis, increased intestinal expression of HMOX-1 has been demonstrated [74].…”

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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Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression

Cited by 64 publications

References 125 publications

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

A Targeted Proteomics Approach Reveals a Serum Protein Signature as Diagnostic Biomarker for Resectable Gastric Cancer

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

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

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