Nonheme Iron-Nitrosyl Complex Formation in Rat Hepatocytes: Detection by Electron Paramagnetic Resonance Spectroscopy

Stadler, J.; Bergonia, Hector A.; Silvio, Mauricio Di; Sweetland, Michael A.; Billiar, T. R.; Simmons, R L; Lancaster, Jack R.

doi:10.1006/abbi.1993.1173

Cited by 120 publications

(72 citation statements)

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“…The cells (2.5 ×105 cells/well in 12-well plates) were washed twice with media and then treated with media containing 2 mM SNAP for 12 h. Cell viability was determined after this treatment by Cresyl violet staining [9]. In vivo activated hepatocytes were isolated 5 days after intraportal injection of rats with killed C. parvum [10].…”

Section: Isolation and Treatment Of Hepatocytesmentioning

confidence: 99%

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Kim

Bergonia

Lancaster³

1995

FEBS Letters

197

110

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Pretreatment of rat hepatocytes with low-dose nitrogen oxide (addition of SNAP in vitro or induction of nitric oxide synthase in vitro or in vivo) imparts resistance to killing and decrease in aconitase and mitochondrial electron transfer from a second exposure to a higher dose of SNAP. Induction of this resistance is prevented by cycloheximide, indicating upregulation of protective protein(s). Ferritin levels are increased as are nonheme iron-NO EPR signals. Tin-protoporphyrin (SnPP) prevents protection, suggesting involvement of hsp32 (heme oxygenase) and/or guanylyl cyclase (GC). Cross-resistance to H2Oz killing is also observed, which is also prevented by cycloheximide and SnPP. Thus, hepatocytes possess inducible protective mechanisms against nitrogen oxide and reactive oxygen toxicity.

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Section: Isolation and Treatment Of Hepatocytesmentioning

confidence: 99%

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Kim

Bergonia

Lancaster³

1995

FEBS Letters

197

110

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“…Such complexes are formed following activation of the iNOS pathway in macrophages (Lancaster & Hibbs, 1990;Pellat et al, 1990) and in their target cells (Drapier et al, 1991), as well as in pancreatic islet fl-cells (Corbett et al, 1991) and hepatocytes (Stadler et al, 1993). It has been proposed that DNIC might contribute to the cytotoxic action of NO, through inhibition of some key mitochondrial enzymes of the respiratory chain (for review see Henry et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Müller

Kleschyov

Stoclet

1996

British J Pharmacology

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1 The aim of this study was to assess whether or not vasoactive nitric oxide (NO) stores exist within vascular tissue after lipopolysaccharide (LPS)-treatment. 2 Rat thoracic aortic rings (for contraction experiments) or whole thoracic aortae (for electron paramagnetic resonance (e.p.r.) spectroscopy) were incubated for 18 h at 370C in the absence (control) or in the presence of LPS (10 ug ml-'), with or without L-arginine (L-Arg, 1 mM), the substrate of NO synthase (NOS) or Nw-nitro-L-arginine methyl ester (L-NAME, 1 mM), an inhibitor of NOS. 3 Incubation of rat aortic rings with LPS and L-Arg resulted in a significant decrease of the maximum contractile response to noradrenaline (NA, 3 uM). Addition of L-NAME (3 mM) enhanced contraction towards control values. After precontraction with NA and L-NAME, addition of N-acetyl-L-cysteine (NAC, 0.1 to 10 mM) evoked a concentration-dependent relaxation in rings incubated with LPS and LArg, but not in control rings, rings incubated with LPS in the absence of L-Arg or rings incubated with LPS in the presence of L-Arg and L-NAME. Removal of the endothelium did not significantly modify the relaxation induced by NAC. Methylene blue (3 puM), an inhibitor of the activation of guanylyl cyclase by NO, completely abolished the relaxing effect of NAC. 4 The presence of protein-bound dinitrosyl non-haem iron complexes (DNIC) was detected by e.p.r. spectroscopy in aortae incubated with LPS and L-Arg, but not in control aortae. Furthermore in LPStreated aortae, addition of NAC (20 mM) gave rise to the appearance of an e.p.r. signal characteristic of low molecular weight DNIC. 5 These results provide evidence that, within vascular tissue, NO generated from L-Arg by LPS-induced NOS activity can be stored as protein-bound DNIC in non-endothelial cells. Upon addition of NAC, low molecular weight DNIC are released from these storage sites and induce vascular relaxation probably through guanylyl cyclase activation.

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“…More than 30 years ago it was discovered that paramagnetic dinitrosyl iron complexes (DNICs) 2 can be formed in biological systems (1). These compounds can be observed in isolated cells or tissues incubated or perfused with NO or NO-generating systems (1)(2)(3)(4)(5), but traces are also present in tissues under physiological conditions (4).…”

mentioning

confidence: 99%

“…These compounds can be observed in isolated cells or tissues incubated or perfused with NO or NO-generating systems (1)(2)(3)(4)(5), but traces are also present in tissues under physiological conditions (4). Such complexes, in which ferrous ion coordinates two nitric oxide molecules together with two other ligands, with characteristic EPR spectra centered at about g ϭ 2.03 made possible their discovery in cells or tissues.…”

mentioning

confidence: 99%

“…Although the natural occurrence of DNICs has been demonstrated unequivocally, their chemical identity in vivo is still ambiguous. In fact, even if DNICs exist as free low molecular mass complexes of the general formula (NO) 2 (RS) 2 Fe, e.g. the dinitrosyl-diglutathionyl iron complex (DNDGIC) and dinitrosyl-dicysteinyl iron complex, the existence of such free complexes in vivo has never been demonstrated; they always appear bound to unknown proteins (1).…”

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confidence: 99%

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Glutathione Transferases Sequester Toxic Dinitrosyl-Iron Complexes in Cells

Pedersen¹,

Maria

Turella

et al. 2007

Journal of Biological Chemistry

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It is now well established that exposure of cells and tissues to nitric oxide leads to the formation of a dinitrosyl-iron complex bound to intracellular proteins, but little is known about how the complex is formed, the identity of the proteins, and the physiological role of this process. By using EPR spectroscopy and enzyme activity measurements to study the mechanism in hepatocytes, we here identify the complex as a dinitrosyl-diglutathionyl-iron complex (DNDGIC) bound to Alpha class glutathione S-transferases (

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Nonheme Iron-Nitrosyl Complex Formation in Rat Hepatocytes: Detection by Electron Paramagnetic Resonance Spectroscopy

Cited by 120 publications

References 0 publications

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Nitrogen oxide‐induced autoprotection in isolated rat hepatocytes

Evidence for N‐acetylcysteine‐sensitive nitric oxide storage as dinitrosyl‐iron complexes in lipopolysaccharide‐treated rat aorta

Glutathione Transferases Sequester Toxic Dinitrosyl-Iron Complexes in Cells

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