Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nature's marvels endowed in gaseous molecules I: Carbon monoxide and its physiological and therapeutic roles.

ABSTRACT: Nature has endowed gaseous molecules such as O₂, CO₂, CO, NO, H₂S, and N₂ with critical and diverse roles in sustaining life, from supplying energy needed to power life and building blocks for life's physical structure to mediating and coordinating cellular functions. In this article, we give a brief introduction of the complex functions of the various gaseous molecules in life and then focus on carbon monoxide as a specific example of an endogenously produced signaling molecule to highlight the importance of this class of molecules. The past twenty years have seen much progress in understanding CO's mechanism(s) of action and pharmacological effects as well as in developing delivery methods for easy administration. One remarkable trait of CO is its pleiotropic effects that have few parallels, except perhaps its sister gaseous signaling molecules such as nitric oxide and hydrogen sulfide. This review will delve into the sophistication of CO-mediated signaling as well as its validated pharmacological functions and possible therapeutic applications.

SUBMITTER: Yang X

PROVIDER: S-EPMC8245769 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Therapeutic applications of carbon monoxide.

Project description:Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models.

| S-EPMC3932177 | biostudies-literature

Therapeutic Aspects of Carbon Monoxide in Cardiovascular Disease.

Project description:Carbon monoxide (CO) is being increasingly recognized as a potential therapeutic with important signaling functions in various diseases. Carbon monoxide-releasing molecules (CORMs) show anti-apoptotic, anti-inflammatory, and anti-oxidant effects on the tissues of organisms, thus contributing to tissue homeostasis. An increase in reactive oxygen species production from the mitochondria after exposure to CO is also considered one of the underlying mechanisms of cardioprotection, although mitochondrial inhibition is the main toxic mechanism of CO poisoning. This review highlights the mechanism of the biological effects of CO and its potential application as a therapeutic in clinical settings, including in cardiovascular diseases. This review also discusses the obstacles and limitations of using exogenous CO or CORMs as a therapeutic option, with respect to acute CO poisoning.

| S-EPMC6121498 | biostudies-literature

A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery.

Project description:We report on the preparation of the first material for therapeutic delivery of CO. A peptide amphiphile was synthesized with a covalently attached ruthenium tricarbonyl. Self-assembled nanofiber gels containing this peptide spontaneously released CO with prolonged release kinetics compared to soluble CO donors. Oxidatively stressed cardiomyocytes had improved viability when treated with this peptide, demonstrating its potential as a biodegradable gel for localized therapeutic CO delivery.

| S-EPMC3374652 | biostudies-literature

A nine-atom rhodium-aluminum oxide cluster oxidizes five carbon monoxide molecules.

Project description:Noble metals can promote the direct participation of lattice oxygen of very stable oxide materials such as aluminum oxide, to oxidize reactant molecules, while the fundamental mechanism of noble metal catalysis is elusive. Here we report that a single atom of rhodium, a powerful noble metal catalyst, can promote the transfer of five oxygen atoms to oxidize carbon monoxide from a nine-atom rhodium-aluminum oxide cluster. This is a sharp improvement in the field of cluster science where the transfer of at most two oxygen atoms from a doped cluster is more commonly observed. Rhodium functions not only as the preferred trapping site to anchor and oxidize carbon monoxide by the oxygen atoms in direct connection with rhodium but also the primarily oxidative centre to accumulate the large amounts of electrons and the polarity of rhodium is ultimately transformed from positive to negative.

| S-EPMC4843021 | biostudies-literature

Reactive oxygen species mediate bactericidal killing elicited by carbon monoxide-releasing molecules.

Project description:CO-releasing molecules (CO-RMs) were previously shown by us to be more potent bactericides than CO gas. This suggests a mechanism of action for CO-RM, which either potentiates the activity of CO or uses another CO-RM-specific effect. We have also reported that CORM-2 induces the expression of genes related to oxidative stress. In the present study we intend to establish whether the generation of reactive oxygen species by CO-RMs may indeed result in the inhibition of bacterial cellular function. We now report that two CO-RMs (CORM-2 and ALF062) stimulate the production of ROS in Escherichia coli, an effect that is abolished by addition of antioxidants. Furthermore, deletion of genes encoding E. coli systems involved in reactive oxygen species scavenging, namely catalases and superoxide dismutases, potentiates the lethality of CORM-2 due to an increase of intracellular ROS content. CORM-2 also induces the expression of the E. coli DNA repair/SOS system recA, and its inactivation enhances toxicity of CORM-2. Moreover, fluorescence microscopy images reveal that CORM-2 causes DNA lesions to bacterial cells. We also demonstrate that cells treated with CORM-2 contain higher levels of free iron arising from destruction of iron-sulfur proteins. Importantly, we show that CO-RMs generate hydroxyl radicals in a cell-free solution, a process that is abolished by scavenging CO. Altogether, we provide a novel insight into the molecular basis of CO-RMs action by showing that their bactericidal properties are linked to cell damage inflicted by the oxidative stress that they are able to generate.

| S-EPMC3143634 | biostudies-literature

Cardioprotection via Metabolism for Rat Heart Preservation Using the High-Pressure Gaseous Mixture of Carbon Monoxide and Oxygen.

Project description:The high-pressure gas (HPG) method with carbon monoxide (CO) and oxygen (O2) mixture maintains the preserved rat heart function. The metabolites of rat hearts preserved using the HPG method (HPG group) and cold storage (CS) method (CS group) by immersion in a stock solution for 24 h were assessed to confirm CO and O2 effects. Lactic acid was significantly lower and citric acid was significantly higher in the HPG group than in the CS group. Moreover, adenosine triphosphate (ATP) levels as well as some pentose phosphate pathway (PPP) metabolites and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were significantly higher in the HPG group than in the CS group. Additionally, reduced glutathione (GSH), which protects cells from oxidative stress, was also significantly higher in the HPG group than in the CS group. These results indicated that each gas, CO and O2, induced the shift from anaerobic to aerobic metabolism, maintaining the energy of ischemic preserved organs, shifting the glucose utilization from glycolysis toward PPP, and reducing oxidative stress. Both CO and O2 in the HPG method have important effects on the ATP supply and decrease oxidative stress for preventing ischemic injury. The HPG method may be useful for clinical application.

| S-EPMC7700337 | biostudies-literature

Molecular Marvels: Small Molecules Paving the Way for Enhanced Gene Therapy.

Project description:In the rapidly evolving landscape of genetic engineering, the advent of CRISPR-Cas technologies has catalyzed a paradigm shift, empowering scientists to manipulate the genetic code with unprecedented accuracy and efficiency. Despite the remarkable capabilities inherent to CRISPR-Cas systems, recent advancements have witnessed the integration of small molecules to augment their functionality, introducing new dimensions to the precision and versatility of gene editing applications. This review delves into the synergy between CRISPR-Cas technologies based specifically on Cas9 and small-molecule drugs, elucidating the pivotal role of chemicals in optimizing target specificity and editing efficiency. By examining a diverse array of applications, ranging from therapeutic interventions to agricultural advancements, we explore how the judicious use of chemicals enhances the precision of CRISPR-Cas9-mediated genetic modifications. In this review, we emphasize the significance of small-molecule drugs in fine-tuning the CRISPR-Cas9 machinery, which allows researchers to exert meticulous control over the editing process. We delve into the mechanisms through which these chemicals bolster target specificity, mitigate off-target effects, and contribute to the overall refinement of gene editing outcomes. Additionally, we discuss the potential of chemical integration in expanding the scope of CRISPR-Cas9 technologies, enabling tailored solutions for diverse genetic manipulation challenges. As CRISPR-Cas9 technologies continue to evolve, the integration of small-molecule drugs emerges as a crucial avenue for advancing the precision and applicability of gene editing techniques. This review not only synthesizes current knowledge but also highlights future prospects, paving the way for a deeper understanding of the synergistic interplay between CRISPR-Cas9 systems and chemical modulators in the pursuit of more controlled and efficient genetic modifications.

| S-EPMC10818943 | biostudies-literature

The bactericidal activity of carbon monoxide-releasing molecules against Helicobacter pylori.

Project description:Helicobacter pylori is a pathogen that establishes long life infections responsible for chronic gastric ulcer diseases and a proved risk factor for gastric carcinoma. The therapeutic properties of carbon-monoxide releasing molecules (CORMs) led us to investigate their effect on H. pylori. We show that H. pylori 26695 is susceptible to two widely used CORMs, namely CORM-2 and CORM-3. Also, several H. pylori clinical isolates were killed by CORM-2, including those resistant to metronidazole. Moreover, sub-lethal doses of CORM-2 combined with metronidazole, amoxicillin and clarithromycin was found to potentiate the effect of the antibiotics. We further demonstrate that the mechanisms underpinning the antimicrobial effect of CORMs involve the inhibition of H. pylori respiration and urease activity. In vivo studies done in key cells of the innate immune system, such as macrophages, showed that CORM-2, either alone or when combined with metronidazole, strongly reduces the ability of H. pylori to infect animal cells. Hence, CORMs have the potential to kill antibiotic resistant strains of H. pylori.

| S-EPMC3873287 | biostudies-other

Genetic and physiological characterization of the Rhodospirillum rubrum carbon monoxide dehydrogenase system.

Project description:A 3.7-kb DNA region encoding part of the Rhodospirillum rubrum CO oxidation (coo) system was identified by using oligonucleotide probes. Sequence analysis of the cloned region indicated four complete or partial open reading frames (ORFs) with acceptable codon usage. The complete ORFs, the 573-bp cooF and the 1,920-bp cooS, encode an Fe/S protein and the Ni-containing carbon monoxide dehydrogenase (CODH), respectively. The four 4-cysteine motifs encoded by cooF are typical of a class of proteins associated with other oxidoreductases, including formate dehydrogenase, nitrate reductase, dimethyl sulfoxide reductase, and hydrogenase activities. The R. rubrum CODH is 67% similar to the beta subunit of the Clostridium thermoaceticum CODH and 47% similar to the alpha subunit of the Methanothrix soehngenii CODH; an alignment of these three peptides shows relatively limited overall conservation. Kanamycin cassette insertions into cooF and cooS resulted in R. rubrum strains devoid of CO-dependent H2 production with little (cooF::kan) or no (cooS::kan) methyl viologen-linked CODH activity in vitro, but did not dramatically alter their photoheterotrophic growth on malate in the presence of CO. Upstream of cooF is a 567-bp partial ORF, designated cooH, that we ascribe to the CO-induced hydrogenase, based on sequence similarity with other hydrogenases and the elimination of CO-dependent H2 production upon introduction of a cassette into this region. From mutant characterizations, we posit that cooH and cooFS are not cotranscribed. The second partial ORF starts 67 bp downstream of cooS and would be capable of encoding 35 amino acids with an ATP-binding site motif.

| S-EPMC206364 | biostudies-other

Different effects of partial pressure in a high-pressure gaseous mixture of carbon monoxide and oxygen for rat heart preservation.

Project description:We maintained the function of an extracted rat heart after 24-48 h preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). Here, we assessed the effects of different partial pressures of hyperbaric CO and O2 for 24-48 h at 4 °C on rat heart preservation and compared conditions including immersion in University of Wisconsin solution. Preserved hearts were transplanted into recipient rats via heterotopic cervical heart transplantation for in vivo evaluation and perfused using the Langendorff system for ex vivo evaluation. The survival rate of transplanted hearts was 100% at postoperative day 7 in the CO + O2 (PCO:PO2 = 1.5:2.0 atm) group but only 33% in the CO + O2 (PCO:PO2 = 2.0:1.5 atm) group. Langendorff system and histopathological analysis revealed that the left ventricular pressure of preserved hearts in the CO + O2 (PCO:PO2 = 1.5:2.0 atm) group was better than the CO + O2 (PCO:PO2 = 2.0:1.5 atm). We demonstrate that exposure of rat hearts to hyperbaric CO and O2 is superior to the immersion method and that partial pressure of hyperbaric CO and O2 is crucial to preservation.

| S-EPMC6522590 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data