scholarly journals Modulation of Human Hydrogen Sulfide Metabolism by Micronutrients, Preliminary Data

2022 ◽  
Vol 15 ◽  
pp. 117863882110653
Author(s):  
Maurizio Dattilo ◽  
Carolina Fontanarosa ◽  
Michele Spinelli ◽  
Vittorio Bini ◽  
Angela Amoresano
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Strong Increase ◽  
Alternative Pathways ◽  
Nitric Oxide Metabolism ◽  
Methylation Capacity ◽  
Health And Disease ◽  
Aged Subjects ◽  
Endogenous Release

Background: Hydrogen sulfide (H2S) is a pivotal gasotransmitter networking with nitric oxide (NO) and carbon monoxide (CO) to regulate basic homeostatic functions. It is released by the alternative pathways of transulfuration by the enzymes Cystathionine Beta Synthase (CBS) and Cystathionine Gamma Lyase (CSE), and by Cysteine AminoTransferase (CAT)/ 3-Mercaptopyruvate Sulfur Transferase (3MPST). A non-enzymatic, intravascular release is also in place. We retrospectively investigated the possibility to modulate the endogenous H2S release and signaling in humans by a dietary manipulation with supplemented micronutrients (L-cystine, Taurine and pyridoxal 5-phopsphate/P5P). Methods: Patients referring for antiaging purposes underwent a 10-day supplementation. Blood was collected at baseline and after treatment and the metabolome was investigated by mass spectrometry to monitor the changes in the metabolites reporting on H2S metabolism and related pathways. Results: Data were available from 6 middle aged subjects (2 women). Micronutrients increased 3-mercaptopyruvate ( P = .03), reporting on the activity of CAT that provides the substrate for H2S release within mitochondria by 3MPST, decreased lanthionine ( P = .024), reporting the release of H2S from CBS, and had no significant effect of H2S release from CSE. This is compatible with a homeostatic balancing. We also recorded a strong increase of reporters of H2S-induced pathways including 5-MethylTHF ( P = .001) and SAME ( P = .022), reporting on methylation capacity, and of BH4 ( P = .021) and BH2 ( P = .028) reporting on nitric oxide metabolism. These activations may be explained by the concomitant induction of non-enzymatic release of H2S. Conclusions: Although the current evidences are weak and will need to be confirmed, the effect of micronutrients was compatible with an increase of the H2S endogenous release and signaling within the control of homeostatic mechanisms, further endorsing the role of feeding in health and disease. These effects might result in a H2S boosting effect in case of defective activity of pathologic origin, which should be checked in duly designed clinical trials.

The Role of Reactive Oxygen Species, Kinases, Hydrogen Sulfide, and Nitric Oxide in the Regulation of Autophagy and Their Impact on Ischemia and Reperfusion Injury in the Heart

2020 ◽  
Vol 16 ◽  
Author(s):  
Andrey Krylatov ◽  
Leonid Maslov ◽  
Sergey Y. Tsibulnikov ◽  
Nikita Voronkov ◽  
Alla Boshchenko ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Hydrogen Sulfide ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Ischemia And Reperfusion ◽  
Oxygen Species ◽  
Ischemia And Reperfusion Injury ◽  
Adaptive Process

: There is considerable evidence in the heart that autophagy in cardiomyocytes is activated by hypoxia/reoxygenation (H/R) or in hearts by ischemia/reperfusion (I/R). Depending upon the experimental model and duration of ischemia, increases in autophagy in this setting maybe beneficial (cardioprotective) or deleterious (exacerbate I/R injury). Aside from the conundrum as to whether or not autophagy is an adaptive process, it is clearly regulated by a number of diverse molecules including reactive oxygen species (ROS), various kinases, hydrogen sulfide (H2S) and nitric oxide (NO). The purpose this review is to address briefly the controversy regarding the role of autophagy in this setting and to examine a variety of disparate molecules that are involved in its regulation.

scholarly journals The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

2020 ◽  
Vol 10 ◽  
Author(s):  
Md. Aejazur Rahman ◽  
Joel N. Glasgow ◽  
Sajid Nadeem ◽  
Vineel P. Reddy ◽  
Ritesh R. Sevalkar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Host Immunity ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Enzymatic Production ◽  
Growth And Survival ◽  
Wide Range

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaoping Liu ◽  
Mohamed A El-Mahdy ◽  
Raed S Ismail ◽  
Sean Little ◽  
Le T Thuy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Wall ◽  
No Donor ◽  
Nitric Oxide Metabolism ◽  
No Consumption ◽  
Potent Vasodilator ◽  
Inner Diameter ◽  
The Difference ◽  
Synthase Inhibitor

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis

2018 ◽  
Vol 234 (7) ◽  
pp. 11411-11423 ◽  
Author(s):  
Mohammad Khabbaz Shirazi ◽  
Asaad Azarnezhad ◽  
Mohammad Foad Abazari ◽  
Mansour Poorebrahim ◽  
Pegah Ghoraeian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Hydrogen Sulfide ◽  
Kidney Disease ◽  
Nitric Oxide Signaling

scholarly journals Endothelin in health and disease

2004 ◽  
Vol 4 (3) ◽  
pp. 31-34 ◽  
Author(s):  
Emina Nakaš-Ićindić ◽  
Asija Začiragić ◽  
Almira Hadžović ◽  
Nešina Avdagić
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Calcium Ions ◽  
Potential Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Health And Disease ◽  
Endothelin 3 ◽  
Stimulation Of

Endothelin is a recently discovered peptide composed of 21 amino acids. There are three endothelin isomers: endothelin -1 (ET-1), endothelin -2 (ET-2) and endothelin - 3 (ET-3). In humans and animals levels of ET-1, ET-2, ET-3 and big endothelin in blood range from 0,3 to 3 pg/ml. ET-1, ET-2 and ET-3 act by binding to receptors. Two main types of the receptors for endothelins exist and they are referred to as A and B type receptors. Different factors can stimulate or inhibit production of endothelin by endothelial cells. Mechanical stimulation of endothehum, thrombin, calcium ions, epinephrine, angiotensin II, vasopressin, dopamine, cytokines, growth factors stimulate the production of endothelin whereas nitric oxide, cyclic guanosine monophosphate, atrial natriuretic peptide, prostacyclin, bradykinin inhibit its production. Endothelins have different physiological roles in human body but at the same time their actions are involved in the pathogenesis of many diseases.The aim of this review was to present some of, so far, the best studied physiological roles of endothelin and to summarize evidence supporting the potential role of ET in the pathogenesis of certain diseases.

scholarly journals Novel insights into the role of nitric oxide and hydrogen sulfide in myocardial protection

2016 ◽  
Author(s):  
Σοφία-Ίρις Μπιμπλή
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Myocardial Protection

Σκοπός: Να διερευνήσουμε το ρόλο των ενδογενών παραγόμενων και εξωγενώς χορηγούμενων αέριων διαβιβαστών, NO και H₂S, i) στη παθοφυσιολογία του εμφράγματος του μυοκαρδίου, ii) στην ικανότητά τους να μιμούνται το PostC και iii) το φυσιολογικό τους ρόλο στο κάπνισμα. Οι σκοποί προσεγγίστηκαν με την διενέργεια τεσσάρων διακριτών μελετών. Μέθοδοι και Αποτελέσματα: Στην πρώτη μελέτη η επαγωγή οξειδωτικού στρες σε καρδιομυοκύτταρα ή η in vivo επαγωγή εμφράγματος του μυοκαρδίου ενεργοποίησε την PYK2 και φωσφορυλίωσε την eNOS τόσο στην ανασταλτική Y656 όσο και στη θέση ενεργοποίησης S1176. Με δοκιμασίες ενεργότητας η θέση Y657 αποδείχθηκε κυρίαρχη σε σχέση με τη θέση S1176. Η φαρμακολογική αναστολή της PYK2 ανέστρεψε την αναστολή, της eNOS και μείωσε την έκταση του εμφράγματος στους μύες άγριου τύπου, αλλά όχι στους eNOS KO μύες. Στη δεύτερη και τρίτη μελέτη η χορήγηση Νιτρογλυκερίνης και NaHS μείωσαν την έκταση του εμφράγματος σε in vivo κονίκλους. Ωστόσο η μοριακή σηματοδότηση των δύο μορίων διαφοροποιήθηκε. Η καρδιοπροστατευτική δράση της νιτρογλυκερίνης ανατράπηκε κατόπιν αναστολής των PI3K και NOS ενώ η χορήγησή της δε μείωσε την έκταση του εμφράγματος σε μύες eNOS KO. Επιπρόσθετα, η Νιτρογλυκερίνη δεν αύξησε τα επίπεδα του καρδιακού cGMP ενώ η αναστολή της PKG δεν ανέτρεψε την προστατευτική της δράση. Μηχανιστικά, η Νιτρογλυκερίνη προστάτευσε μέσω ενός εξαρτώμενου από την CypD τρόπου καθώς δεν οδήγησε σε επιπρόσθετη προστασία σε CypD KO μύες. Ενδιαφέρον αποτελεί το γεγονός ότι η δράση της σχετίστηκε με μία εξαρτώμενη από την eNOS μείωση του νιτρο-οξειδωτικού στρες. Αντίθετα η αναστολή των NOS δεν επηρέασε την ευεργετική δράση του NaHS στην ομάδα των κονίκλων, ωστόσο, στους μύες η γενετική ή φαρμακολογική αναστολή της eNOS ανέτρεψε τη δράση του NaHS. Το NaHS αύξησε τα καρδιακά επίπεδα του cGMP και η αναστολή της PKG ανέστρεψε την προστατευτική του δράση. Επιπρόσθετα, το NaHS ενεργοποίησε τη φωσφολαμβάνη (PLN), με τρόπο εξαρτώμενο από την PKG και δεν μείωσε την έκταση του εμφράγματος σε μύες PLN KO. Στην τέταρτη μελέτη η έκθεση μυών σε καπνό τσιγάρου αύξησε την αρτηριακή πίεση και ενεργοποίησε το μονοπάτι NOS/sGC/cGMP ενώ μείωσε την έκφραση των ενζύμων που παράγουν H2S. Η έκθεση στο κάπνισμα δεν αύξησε την έκταση του εμφράγματος σε σχέση με την ομάδα έκθεσης σε αέρα δωματίου. Η εφαρμογή του PreC αλλά όχι του PostC ήταν αποτελεσματική στους μύες υπό έκθεση σε καπνό τσιγάρου. Το PreC διατήρησε την καρδιοπροστατευτική του δράση καθώς δεν επηρέασε την σηματοδότηση επιβίωσης σε αντίθεση με το PostC. Συμπεράσματα: i) η PYK2 αποτελεί κυρίαρχο ρυθμιστή της eNOS στο έμφραγμα του μυοκαρδίου; ii) Η εξωγενής χορήγηση δοτών ΝΟ και H₂S μειώνει την έκταση του εμφράγματος. Οι δύο αέριοι διαβιβαστές λειτουργούν με διακριτό μοριακό μηχανισμό, ωστόσο αμφότεροι διατηρούν την καρδιακή μιτοχονδριακή ακεραιότητα και iii) Το κάπνισμα αποτελεί μία νέα συννοσυρότητα η οποία αναστέλλει την ευεργετική δράση του PostC στο μυοκάρδιο επιδρώντας στα σηματοδοτικά μονοπάτια διάσωσης.

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