Reaction Mechanisms of HS Oxidation by Naphthoquinones.

1,4-naphthoquinones (NQs) catalytically oxidize HS to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine HS oxidation by NQs with various substituent groups. In general, the order of HS oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions.

Coenzyme Q and related quinones oxidize HS to polysulfides and thiosulfate.

In the canonical pathway for mitochondrial HS oxidation electrons are transferred from sulfide:quinone oxidoreductase (SQR) to complex III via ubiquinone (CoQ). We previously observed that a number of quinones directly oxidize HS and we hypothesize that CoQ may have similar properties. Here we examine HS oxidation by CoQ and more hydrophilic, truncated forms, CoQ and CoQ, in buffer using HS and polysulfide fluorophores (AzMC and SSP4), silver nanoparticles to measure thiosulfate (HSO), mass spectrometry to identify polysulfides and O-sensitive optodes to measure O consumption.

'Antioxidant' berries, anthocyanins, resveratrol and rosmarinic acid oxidize hydrogen sulfide to polysulfides and thiosulfate: A novel mechanism underlying their biological actions.

Nutraceutical polyphenol catechins in green tea oxidize HS to polysulfides (PS) in buffer and in cells thereby conveying their cytoprotective effects. Here we measure HS oxidation in buffer and HEK293 cells by over-the-counter nutraceuticals, blueberry, bilberry and cranberry, and by polyphenols, cyanadin (Cya), quercetin (Que), rosmarinic acid (RA) and resveratrol (Res). HS and PS were measured with specific fluorophores, AzMc and SSP4 respectively, and thiosulfate (TS) production was measured in buffer using silver nanoparticles (AgNPs).

Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects.

We have shown that autoxidized polyphenolic nutraceuticals oxidize HS to polysulfides and thiosulfate and this may convey their cytoprotective effects. Polyphenol reactivity is largely attributed to the B ring, which is usually a form of hydroxyquinone (HQ). Here, we examine the effects of HQs on sulfur metabolism using HS- and polysulfide-specific fluorophores (AzMC and SSP4, respectively) and thiosulfate sensitive silver nanoparticles (AgNP).

Effects of Manganese Porphyrins on Cellular Sulfur Metabolism.

Manganese porphyrins (MnPs), MnTE-2-PyP, MnTnHex-2-PyP and MnTnBuOE-2-PyP, are superoxide dismutase (SOD) mimetics and form a redox cycle between O and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (HO). We previously found that MnPs oxidize hydrogen sulfide (HS) to polysulfides (PS; HS, n = 2-6) in buffer. Here, we examine the effects of MnPs for 24 h on HS metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using HS (AzMC, MeRho-AZ) and PS (SSP4) fluorophores.

Are the beneficial effects of 'antioxidant' lipoic acid mediated through metabolism of reactive sulfur species?

The health benefits of lipoic acid (LA) are generally attributed to mitigating the harmful effects of reactive oxygen species (ROS). ROS are chemically similar to reactive sulfur species (RSS) and signal through identical mechanisms. Here we examined the effects of LA on RSS in HEK293 cells using HS and polysulfide (PS) specific fluorophores, AzMC and SSP4.

Metabolism of hydrogen sulfide (HS) and Production of Reactive Sulfur Species (RSS) by superoxide dismutase.

Reactive sulfur species (RSS) such as HS, HS, HS, (n = 2-7) and HS are chemically similar to HO and the reactive oxygen species (ROS) HO, HO, O and act on common biological effectors. RSS were present in evolution long before ROS, and because both are metabolized by catalase it has been suggested that "antioxidant" enzymes originally evolved to regulate RSS and may continue to do so today. Here we examined RSS metabolism by Cu/Zn superoxide dismutase (SOD) using amperometric electrodes for dissolved HS, a polysulfide-specific fluorescent probe (SSP4), and mass spectrometry to identify specific polysulfides (HS-HS).

Fluorescence quenching by metal centered porphyrins and poryphyrin enzymes.

Fluorescence spectroscopy and microscopy have been used extensively to monitor biomolecules, especially reactive oxygen species (ROS) and, more recently, reactive sulfide (RSS) species. Nearly all fluorophores are either excited by or emit light between 450 and 550 nm, which is similar to the absorbance of heme proteins and metal-centered porphyrins. Here we examined the effects of catalase (Cat), reduced and oxidized hemoglobin (Hb and metHb), albumin (alb), manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP), iron protoporphyrin IX (hemin), and copper protoporphyrin IX (CuPPIX) on the fluorescence properties of fluorescein.

Garlic oil polysulfides: H2S- and O2-independent prooxidants in buffer and antioxidants in cells.

The health benefits of garlic and other organosulfur-containing foods are well recognized and have been attributed to both prooxidant and antioxidant activities. The effects of garlic are surprisingly similar to those of hydrogen sulfide (H2S), which is also known to be released from garlic under certain conditions. However, recent evidence suggests that polysulfides, not H2S, may be the actual mediator of physiological signaling.

A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter.

Thiosulfate: a readily accessible source of hydrogen sulfide in oxygen sensing.

H2S derived from organic thiol metabolism has been proposed serve as an oxygen sensor in a variety of systems because of its susceptibility to oxidation and its ability to mimic hypoxic responses in numerous oxygen-sensing tissues. Thiosulfate, an intermediate in oxidative H2S metabolism can alternatively be reduced and regenerate H2S. We propose that this contributes to the H2S-mediated oxygen-sensing mechanism.

Hydrogen sulfide is an oxygen sensor in the carotid body.

There is considerable controversy surrounding the initial step that transduces a fall in [Formula: see text] into a physiological signal, i.e., the "oxygen sensor" in chemoreceptors.

Hydrogen sulfide and oxygen sensing in the cardiovascular system.

Vertebrate cardiorespiratory homeostasis is inextricably dependent upon specialized cells that provide feedback on oxygen status in the tissues, blood, and on occasion, environment. These "oxygen sensing" cells include chemoreceptors and oxygen-sensitive chromaffin cells that initiate cardiorespiratory reflexes, vascular smooth muscle cells that adjust perfusion to metabolism or ventilation, and other cells that condition themselves in response to episodic hypoxia. Identification of how these cells sense oxygen and transduce this into the appropriate physiological response has enormous clinical applicability, but despite intense research there is no consensus regarding the initial hypoxia-effector coupling mechanism.

Hydrogen sulfide and oxygen sensing: implications in cardiorespiratory control.

Although all cells are variously affected by oxygen, a few have the responsibility of monitoring oxygen tensions and initiating key homeostatic responses when P(O2) falls to critical levels. These ;oxygen-sensing' cells include the chemoreceptors in the gills (neuroepithelial cells), airways (neuroepithelial bodies) and vasculature (carotid bodies) that initiate cardiorespiratory reflexes, oxygen sensitive chromaffin cells associated with systemic veins or adrenal glands that regulate the rate of catecholamine secretion, and vascular smooth muscle cells capable of increasing blood flow to systemic tissues, or decreasing it through the lungs. In spite of intense research, and enormous clinical applicability, there is little, if any, consensus regarding the mechanism of how these cells sense oxygen and transduce this into the appropriate physiological response.

Comparative physiology of the piscine natriuretic peptide system.

The natriuretic peptide (NP) family is a seemingly ubiquitous sodium and volume reducing endocrine system of predominantly cardiac origin. Members of the NP system include ANP, BNP, CNP, VNP, their guanylate cyclase (GC)-linked receptors (NPR-A and NPR-B), and clearance receptor (NPR-C). Through the activation of their membrane-bound GC receptors, these small peptides modulate cellular functions that affect both salt and water balance.

Effects of hypoxia on vertebrate blood vessels.

Hypoxia contracts mammalian respiratory vessels and increases vascular resistance in respiratory tissues of many vertebrates. In systemic vessels these responses vary, hypoxia relaxes mammalian vessels and contracts systemic arteries from cyclostomes. It has been proposed that hypoxic vasoconstriction in cyclostome systemic arteries is the antecedent to mammalian hypoxic pulmonary vasoconstriction, however, phylogenetic characterization of hypoxic responses is lacking.

Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle.

Hydrogen sulfide (H2S) is a recently identified gasotransmitter that may mediate hypoxic responses in vascular smooth muscle. H2S also appears to be a signaling molecule in mammalian non-vascular smooth muscle, but its existence and function in non-mammalian non-vascular smooth muscle have not been examined. In the present study we examined H2S production and its physiological effects in urinary bladder from steelhead and rainbow trout (Oncorhynchus mykiss) and evaluated the relationship between H2S and hypoxia.

Effect of pH on trout blood vessels and gill vascular resistance.

pH is recognized as a modulator of vascular smooth muscle (VSM) tone in mammalian vessels, but little is known about its effects on fish VSM. We investigated the effects of extracellular and intracellular pH (pH(o) and pH(i), respectively) on isolated vessels from steelhead and rainbow trout (Oncorhynchus mykiss, Skamania and Kamloops strains, respectively) and of pH(o) on perfused gills from rainbow trout. In otherwise unstimulated (resting) efferent branchial (EBA) and coeliaco-mesenteric arteries (CMA), anterior cardinal veins (ACV) and perfused gills, increasing pH(o) from 6.

Ultrastructure of the maternal-fetal interface of the yolk sac placenta in sharks.

The blacknose shark, Carcharhinus acronotus, is a viviparous anamniote that develops an epitheliochorial yolk sac placenta. The fetal portion of the uteroplacental complex consists of a proximal portion that forms saccular evaginations. The cells are bilayered stratified squamous with surface microvilli and a high concentration of cytoplasmic filaments.

Lesions that simulate gunshot wounds - further examples II.

A variety of postmortem and antemortem defects may be misinterpreted as gunshot wounds. In this paper, we present an additional series of lesions that simulate gunshot wounds. We briefly discuss each case, emphasizing various aspects of the scene investigation, clinical correlation and autopsy that are important in each case.

Vascular actions of hydrogen sulfide in nonmammalian vertebrates.

Hydrogen sulfide (H(2)S) vasoactivity has been observed in isolated vessels from all vertebrate classes, and its effects, which include constriction, dilation, and multiphasic responses, are both species- and vessel-specific. H(2)S is synthesized by mammalian and fish vessels, and because plasma H(2)S titers are also vasoactive in vitro, it is likely that H(2)S is a tonic effector of cardiovascular homeostasis in many vertebrates. Mechanisms of H(2)S vasoactivity in nonmammalian vertebrates have been limited to the trout where the triphasic relaxation-contraction-relaxation includes endothelium-dependent and -independent components, ATP-dependent K(+) channels, and extracellular and intracellular Ca(2+), all independent of cyclic GMP production.

Death due to Ehlers-Danlos syndrome type IV.

Ehlers-Danlos syndrome (EDS) represents a group of collagen connective tissue disorders characterized by joint laxity, easy bruising, and various skin manifestations. Persons with type IV EDS are at risk for gastrointestinal, uterine, and arterial rupture. Mutations in the COL3A1 gene that encodes for type III procollagen underlie the pathologic abnormalities.

Phosphorylation of thymidine and AZT in heart mitochondria: elucidation of a novel mechanism of AZT cardiotoxicity.

Antiretroviral nucleoside analogs used in highly active antiretroviral therapy (HAART) are associated with cardiovascular and other tissue toxicity associated with mitochondrial DNA depletion, suggesting a block in mitochondrial (mt)-DNA replication. Because the triphosphate forms of these analogs variably inhibit mt-DNA polymerase, this enzyme has been promoted as the major target of toxicity associated with HAART. We have used isolated mitochondria from rat heart to study the mitochondrial transport and phosphorylation of thymidine and AZT (azidothymidine, or zidovudine), a component used in HAART.