The Janus face of alcohol dehydrogenase 3

Staab, Claudia A.; Ålander, Johan; Morgenstern, Ralf; Grafström, Roland C.; Höög, Jan‐Olov

doi:10.1016/j.cbi.2008.10.050

Cited by 42 publications

(42 citation statements)

References 43 publications

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“…A role for glutathione (GSH) in this cascade is supported by the reported alteration in intraerythrocytic SNO metabolism as a function of extra-erythrocytic GSH (64) (Fig. 3A), as well as by studies of the enzyme GSNOR (181,183,257). Specifically, transgenic mice lacking GSNOR accumulate intraerythrocytic SNOs (182) and exhibit reduced peripheral vascular tone (177), suggesting a role for GSH in SNO export from RBCs.…”

Section: Mechanism Of No Export From Rbcs: Role Of Ae-1 and Receptor mentioning

confidence: 87%

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

Doctor

Stamler

2011

Comprehensive Physiology

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The trapping, processing, and delivery of nitric oxide (NO) bioactivity by red blood cells (RBCs) have emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We present here an expanded paradigm for the human respiratory cycle based on the coordinated transport of three gases: NO, O₂, and CO₂. By linking O₂ and NO flux, RBCs couple vessel caliber (and thus blood flow) to O₂ availability in the lung and to O₂ need in the periphery. The elements required for regulated O₂-based signal transduction via controlled NO processing within RBCs are presented herein, including S-nitrosothiol (SNO) synthesis by hemoglobin and O₂-regulated delivery of NO bioactivity (capture, activation, and delivery of NO groups at sites remote from NO synthesis by NO synthase). The role of NO transport in the respiratory cycle at molecular, microcirculatory, and system levels is reviewed. We elucidate the mechanism through which regulated NO transport in blood supports O₂ homeostasis, not only through adaptive regulation of regional systemic blood flow but also by optimizing ventilation-perfusion matching in the lung. Furthermore, we discuss the role of NO transport in the central control of breathing and in baroreceptor control of blood pressure, which subserve O₂ supply to tissue. Additionally, malfunctions of this transport and signaling system that are implicated in a wide array of human pathophysiologies are described. Understanding the (dys)function of NO processing in blood is a prerequisite for the development of novel therapies that target the vasoactive capacities of RBCs.

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Section: Mechanism Of No Export From Rbcs: Role Of Ae-1 and Receptor mentioning

confidence: 87%

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

Doctor

Stamler

2011

Comprehensive Physiology

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“…In addition, RSNOs are substrates for a variety of enzymes including glutathione peroxidase (Freedman et al, 1995), a copper (I)-dependent enzyme (Gordge et al, 1996), g-glutamyl transferase (Hogg et al, 1997), thioredoxin reductase (Nikitovic and Holmgren, 1996), superoxide dismutase (Jourd'heuil et al, 1999), protein disulphide isomerase (Sliskovic et al, 2005), cytoplasmic metalloprotein (Mani et al, 2006) and GSNO reductase (glutathione-dependent formaldehyde reductase, or alcohol dehydrogenase 3) (Liu et al, 2001;. This latter enzyme appears to play a crucial role in regulating nitrosative stress via adjustment of intracellular levels of S-nitrosylated proteins (Foster et al, 2009;Staab et al, 2009); however, there is no direct evidence yet for a role in the transfer of NO signalling from extracellular RSNOs.…”

Section: Cellular Metabolism Of Rsnosmentioning

confidence: 99%

S‐nitrosothiols as selective antithrombotic agents – possible mechanisms

Gordge¹,

Xiao²

2010

British J Pharmacology

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S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progress in understanding how nitric oxide (NO)-related signalling is delivered into cells from stable S-nitrosothiol compounds has revealed a variety of pathways, in particular denitrosation by enzymes located at the cell surface, and transport of intact S-nitrosocysteine via the amino acid transporter system-L (L-AT). Differences in the role of these pathways in platelets and vascular cells may in part explain the reported platelet-selective action. In addition, emerging evidence that S-nitrosothiols regulate key targets on the exofacial surfaces of cells involved in the thrombotic process (for example, protein disulphide isomerase, integrins and tissue factor) suggests novel antithrombotic actions, which may not even require transmembrane delivery of NO.

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“…Formaldehyde exposure induces similar pathological responses as those observed in allergen studies, including thickening and eosinophilia in rodent lungs as well as increases in ADH3 mRNA and GSNO breakdown (Jung et al, 2007;Yi et al, 2007). As an ADH3 substrate, formaldehyde can also accelerate ADH3-mediated GSNO reduction via NAD ϩ /NADH cofactor recycling (Staab et al, 2008(Staab et al, , 2009. These data indicate that formaldehyde, like antigens, can increase ADH3 expression and activity in airways and thus influence pulmonary physiology by altering nitrosothiol levels (Thompson and Grafstrom, 2008;.…”

Section: Thompson Et Almentioning

confidence: 79%

“…Dysregulation of nitrosothiol signaling is also implicated in diseases of the central nervous system, cardiovascular system, and lung (Henderson and Gaston, 2005;Gaston et al, 2006;Pannu and Singh, 2006;Schonhoff et al, 2006;Wu et al, 2007;Lima et al, 2009a;Moore et al, 2009). The derangement of nitrosothiol homeostasis in response to formaldehyde has been suggested and demonstrated experimentally (Yi et al, 2007;Staab et al, 2008Staab et al, , 2009Thompson and Grafstrom, 2008;. It is clear that the distribution, ontogeny, and regulation of ADH3 have important implications for the clearance of endogenous and exogenous formaldehyde, as well as the regulation and modulation of NO signaling pathways.…”

mentioning

confidence: 96%

The Ontogeny, Distribution, and Regulation of Alcohol Dehydrogenase 3: Implications for Pulmonary Physiology

Thompson

Sonawane²,

Grafström³

2009

Drug Metab Dispos

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ABSTRACT:Class III alcohol dehydrogenase (ADH3), also termed formaldehyde dehydrogenase or S-nitrosoglutathione reductase, plays a critical role in the enzymatic oxidation of formaldehyde and reduction of nitrosothiols that regulate bronchial tone. Considering reported associations between formaldehyde vapor exposure and childhood asthma risk, and thus potential involvement of ADH3, we reviewed the ontogeny, distribution, and regulation of mammalian ADH3. Recent studies indicate that multiple biological and chemical stimuli influence expression and activity of ADH3, including the feedback regulation of nitrosothiol metabolism. The levels of ADH3 correlate with, and potentially influence, bronchial tone; however, data gaps remain with respect to the expression of ADH3 during postnatal and early childhood development. Consideration of ADH3 function relative to the respiratory effects of formaldehyde, as well as to other chemical and biological exposures that might act in an additive or synergistic manner with formaldehyde, might be critical to gain better insight into the association between formaldehyde exposure and childhood asthma.

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The Janus face of alcohol dehydrogenase 3

Cited by 42 publications

References 43 publications

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle

S‐nitrosothiols as selective antithrombotic agents – possible mechanisms

The Ontogeny, Distribution, and Regulation of Alcohol Dehydrogenase 3: Implications for Pulmonary Physiology

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