scholarly journals Hydropersulfides (RSSH) and Nitric Oxide (NO) Signaling: Possible Effects on S-Nitrosothiols (RS-NO)

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 169
Author(s):  
Jon M. Fukuto ◽  
Cristina Perez-Ternero ◽  
Jessica Zarenkiewicz ◽  
Joseph Lin ◽  
Adrian J. Hobbs ◽  
...  

S-Nitrosothiol (RS-NO) formation in proteins and peptides have been implicated as factors in the etiology of many diseases and as possible regulators of thiol protein function. They have also been proposed as possible storage forms of nitric oxide (NO). However, despite their proposed functions/roles, there appears to be little consensus regarding the physiological mechanisms of RS-NO formation and degradation. Hydropersulfides (RSSH) have recently been discovered as endogenously generated species with unique reactivity. One important reaction of RSSH is with RS-NO, which leads to the degradation of RS-NO as well as the release of NO. Thus, it can be speculated that RSSH can be a factor in the regulation of steady-state RS-NO levels, and therefore may be important in RS-NO (patho)physiology. Moreover, RSSH-mediated NO release from RS-NO may be a possible mechanism allowing RS-NO to serve as a storage form of NO.

2000 ◽  
Vol 381 (7) ◽  
pp. 575-582 ◽  
Author(s):  
Petra Meineke ◽  
Ursula Rauen ◽  
Herbert de Groot ◽  
Hans-Gert Korth ◽  
Reiner Sustmann

Abstract Fluorescent Nitric Oxide Cheletropic Traps (FNOCTs) were applied to specifically trap nitric oxide (NO) with high sensitivity. The fluorescent oquinoid ?electron system of the FNOCTs (? = 460 nm, ? = 600 nm) reacts rapidly with NO to a fluorescent phenanthrene system (? = 380 nm, ? = 460 nm). The cyclic nitroxides thus formed react further to nonradical products which exhibit identical fluorescence properties. Using the acid form of the trap (FNOCT-4), NO release by spermine NONOate and by lipopolysaccharide (LPS) activated alveolar macrophages were studied. A maximum extracellular release of NO of 37.5 nmol h[-1] (10[6] cells)[-1] from the macrophages was determined at 11 h after activation. Furthermore, intracellular NO release by LPSactivated macrophages and by microvascular omentum endothelial cells stimulated by the Ca[2+] ionophore A-23187, respectively, was monitored on the single cell level by means of fluorescence microscopy. After loading the cells with the membranepermeating acetoxymethylester derivative FNOCT-5,which is hydrolyzed to a nonpermeating dicarboxylate by intracellular hydrolases, NO formation by the endothelial cells started immediately upon stimulation, whereas start of NO production by the macrophages was delayed with a variation between 4 and 8 h for individual cells. These results demonstrate that the FNOCTs can be used to monitor NO release from single cells, as well as from NOdonating compounds, with high sensitivity and with temporal and spatial resolution.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Woan-Yi Wang ◽  
Min-Hsuan Hsu ◽  
Po-Tsung Kao ◽  
Chih-Hung Wang ◽  
...  

Introduction: Cerebral vasoconstriction in the post-resuscitation phase worsens neurological outcome. Nitric oxide (NO) plays important roles mediating vasodilatation and anti-apoptotic protection. We therefore designed an Au-polymersomes/S-nitrosoglutathione (Au-PLGA/GSNO) nanoparticle that can be triggered by ultrasound (US) to release NO, and investigated its roles in mitigating cerebral vasoconstriction and neuronal apoptosis post-CPR. Hypothesis: Spatiotemporally controlled, US-triggered NO release by Au-PLGA/GSNO improves post-CPR cerebral perfusion and confers anti-apoptotic neuroprotection. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, Au-PLGA/GSNO (7500 PPM, 0.4 ml) was infused with simultaneous US (1 MHz) stimulation at the brain 10 min after ROSC. Brain tissue perfusion was continuously recorded by OxyFLO probe and cerebral vasculature videoed by CytoCam. The blood was sampled 2 h post-CPR for measurement of nitrate/nitrite, and the brain harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). In a subgroup the brain was harvested at 24 h for TUNEL stain. Results: After CPR, marked cerebral vasoconstriction was noted on CytoCam while brain perfusion significantly reduced to ~0.5 folds that of baseline. After Au-PLGA/GSNO infusion and US stimulation, cerebral vasoconstriction was ameliorated and the brain perfusion significantly enhanced ( P < 0.05 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P < 0.01) while cleaved caspase-3/caspase-3 of the brain markedly reduced ( P < 0.001). TUNEL stain of the hippocampus CA1 and CA3 regions were also remarkably abrogated, suggesting anti-apoptotic neuroprotection. Specifically, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were also increased ( P < 0.01 and 0.001, respectively), indicating reciprocating activation of Akt-eNOS signaling upstream of NO. Conclusion: Spatiotemporally controlled US-triggered NO release by Au-PLGA/GSNO mitigates cerebral vasoconstriction, improves brain perfusion and confers anti-apoptotic neuroprotection post-CPR via reciprocating Akt-eNOS-NO signaling.


2009 ◽  
Vol 418 (3) ◽  
pp. 673-682 ◽  
Author(s):  
Ivan Mikula ◽  
Suzanne Durocher ◽  
Pavel Martasek ◽  
Bulent Mutus ◽  
Anny Slama-Schwok

Nitrite (NO2−) recycling to nitric oxide (NO) is catalysed by a number of enzymes and induces a protective vasodilation effect under hypoxia/ischaemia. In the present work, we tested the in vitro ability of the three NOS (nitric oxide synthase) isoforms to release NO from nitrite under anoxia using electrochemical detection, chemiluminescence and absorption spectroscopy. The release of free NO from anoxic nitrite solutions at 15 μM was specific to the endothelial NOS isoform (eNOS) and did not occur with the neuronal (nNOS) or inducible (iNOS) isoforms. Unlike xanthine oxidase, the eNOS reductase domain did not recycle nitrite to NO, and wild-type eNOS did not reduce nitrate. Our data suggest that structural and, by inference, dynamic differences between nNOS and eNOS in the distal haem side account for eNOS being the only isoform capable of converting nitrite into NO at pH 7.6. In human dermal microvascular endothelial cells under careful control of oxygen tension, the rates of NO formation determined by chemiluminescence were enhanced ∼3.6- and ∼8.3-fold under hypoxia (2 p.p.m. O2) and anoxia (argon) respectively compared with normoxia (∼22 p.p.m. O2) using 10 μM extracellular nitrite. NOS inhibitors inhibited this hypoxic NO release. Our data show that eNOS is unique in that it releases NO under all oxygen levels from normoxia to complete anoxia at physiological micromolar nitrite concentrations. The magnitude of the hypoxic NO release by the endothelial cells suggest that the endothelium could provide an appropriate response to acute episodic ischaemia and may explain the observed eNOS-expression-specific protective effect as a short-term response in animal models of acute hypoxia.


2014 ◽  
Vol 395 (6) ◽  
pp. 631-639 ◽  
Author(s):  
Jesús Tejero ◽  
Mark T. Gladwin

Abstract Globin proteins are ubiquitous in living organisms and carry out a variety of functions related to the ability of their prosthetic heme group to bind gaseous ligands, such as oxygen, nitric oxide (NO), and CO. Moreover, they catalyze important reactions with nitrogen oxide species, such as NO dioxygenation and nitrite reduction. The formation of NO from nitrite is a reaction catalyzed by globins that has received increasing attention due to its potential as a hypoxic NO signaling mechanism. In this review, we revisit the current knowledge about the role of globins in NO formation and its physiological implications.


1990 ◽  
Vol 265 (20) ◽  
pp. 11535-11538 ◽  
Author(s):  
J Goretski ◽  
O C Zafiriou ◽  
T C Hollocher
Keyword(s):  

1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.


2007 ◽  
Vol 292 (4) ◽  
pp. H1995-H2003 ◽  
Author(s):  
Zuo-Hui Shao ◽  
Wei-Tien Chang ◽  
Kim Chai Chan ◽  
Kim R. Wojcik ◽  
Chin-Wang Hsu ◽  
...  

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 ± 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 ± 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 ± 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 ± 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor Nω-nitro-l-arginine methyl ester (200 μM) reversed these changes and abrogated hypothermia protection. In addition, the PKCε inhibitor myr-PKCε v1-2 (5 μM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cε; nitric oxide synthase.


2009 ◽  
Vol 106 (38) ◽  
pp. 16221-16226 ◽  
Author(s):  
T. Agapie ◽  
S. Suseno ◽  
J. J. Woodward ◽  
S. Stoll ◽  
R. D. Britt ◽  
...  

2013 ◽  
Vol 210 (7) ◽  
pp. 1433-1445 ◽  
Author(s):  
Nataša Obermajer ◽  
Jeffrey L. Wong ◽  
Robert P. Edwards ◽  
Kong Chen ◽  
Melanie Scott ◽  
...  

Nitric oxide (NO) is a ubiquitous mediator of inflammation and immunity, involved in the pathogenesis and control of infectious diseases, autoimmunity, and cancer. We observed that the expression of nitric oxide synthase-2 (NOS2/iNOS) positively correlates with Th17 responses in patients with ovarian cancer (OvCa). Although high concentrations of exogenous NO indiscriminately suppress the proliferation and differentiation of Th1, Th2, and Th17 cells, the physiological NO concentrations produced by patients’ myeloid-derived suppressor cells (MDSCs) support the development of RORγt(Rorc)+IL-23R+IL-17+ Th17 cells. Moreover, the development of Th17 cells from naive-, memory-, or tumor-infiltrating CD4+ T cells, driven by IL-1β/IL-6/IL-23/NO-producing MDSCs or by recombinant cytokines (IL-1β/IL-6/IL-23), is associated with the induction of endogenous NOS2 and NO production, and critically depends on NOS2 activity and the canonical cyclic guanosine monophosphate (cGMP)–cGMP-dependent protein kinase (cGK) pathway of NO signaling within CD4+ T cells. Inhibition of NOS2 or cGMP–cGK signaling abolishes the de novo induction of Th17 cells and selectively suppresses IL-17 production by established Th17 cells isolated from OvCa patients. Our data indicate that, apart from its previously recognized role as an effector mediator of Th17-associated inflammation, NO is also critically required for the induction and stability of human Th17 responses, providing new targets to manipulate Th17 responses in cancer, autoimmunity, and inflammatory diseases.


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