Electron Spin Resonance Analysis of Heme-Nitrosyl and Reduced Iron-Sulfur Centered Complexes in Allogeneic, Heterotopic Cardiac Transplants: Effects of Treatment with Pyrrolidine Dithiocarbamate

Nakanishi, Akemi; Roza, Allan M.; Adams, Mark B.; Seibel, Ross; Moore-Hilton, Gail; Kalyanaraman, Balaraman; Pieper, Galen M.

doi:10.1016/s0891-5849(98)00051-3

Cited by 17 publications

(9 citation statements)

References 30 publications

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“…2). For isografts, signals were observed at g ϭ 2.004 (denoted as a semiquinone radical) and g ϭ 2.02 and 1.94 (denoted as Fe-S cluster protein) (12). These signals are identical to that seen by our laboratory in normal hearts and denoted as background signals (not shown).…”

Section: Resultssupporting

confidence: 65%

“…Previously, we (7,12,21) and other investigators (10,24) have detected by EPR spectroscopy the nitrosylation of myocardial heme protein before rejection in untreated cardiac allografts. Two studies described the formation of dinitrosyl-iron complexes of non-heme protein that was characterized by a specific Fig.…”

Section: Discussionmentioning

confidence: 84%

“…In contrast, in the setting of excess NO production via iNOS, it is possible that molecular interactions of NO with iron-containing proteins may lead to altered cell function or cell injury. Indeed, nitrosylation of heme protein (notably myoglobin) has been demonstrated by EPR spectroscopy in acute cardiac allograft rejection (10)(11)(12). EPR signals for nitrosylated heme protein are found in allograft tissue but not isograft tissue, suggesting that the increase in nitrosylation is due to alloimmune activation rather than secondarily to artifacts of surgery.…”

mentioning

confidence: 99%

“…The cause-effect relationship in nitrosylation of heme protein on graft function during rejection is incompletely understood. Nevertheless, intervention with NOS inhibitors (11,12) or NO scavengers (5-7) that decreased heme nitrosylation also decreased histological rejection scores and prolonged graft survival.…”

mentioning

confidence: 99%

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Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Pieper

Halligan

Hilton

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Section: Resultssupporting

confidence: 65%

Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Pieper

Halligan

Hilton

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…In the first experiment, pyrrolidine dithiocarbamate, an iron-chelator, prolonged grafts survival and inhibited down-stream effects on nitrosylation of myocardial heme protein [48,49]. While this agent inhibited NF-κB binding activity, it was not determined whether the decreased heme protein nitrosylation was due secondarily to NO scavenging or to decreased iNOS protein expression.…”

Section: Evidence Using No Neutralizing Agentsmentioning

confidence: 99%

The complex role of iNOS in acutely rejecting cardiac transplants

Pieper

Roza

2008

Free Radical Biology and Medicine

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This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutelyrejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed.

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Mechanism of Nitrosylmyoglobin Autoxidation: Temperature and Oxygen Pressure Effects on the Two Consecutive Reactions

Møller¹,

Skibsted²

2004

Chemistry A European J

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As shown by singular value decomposition and global analysis of the absorption spectra, oxidation of nitrosylmyoglobin, MbFe(II)NO, by oxygen occurs in two consecutive (pseudo) first-order reactions in aqueous air- saturated solutions at physiological conditions (pH 7.0, I=0.16 m (NaCl)). Both reaction steps have a large temperature dependence with the following activation parameters: DeltaS++(1) = 121+/-7 and DeltaS++(1) = 23+/-29; and DeltaS++(2) = 88+/-14 kJ mol(-1) and DeltaS++(2)-63+/-51 J(-1) K(-1) mol(-1) at 25 degrees C for the first and second step, respectively. At physiological temperature, the initial reaction is faster, while at lower temperatures, the first reaction is slower and rate-determining. The rate of the first reaction is linearly dependent on oxygen pressure at lower pressures, while for oxygen pressures above atmospheric, the rate exhibits saturation behaviour. The second reaction is independent of oxygen pressure. The rate of the second reaction increases when oxymyoglobin is added. In contrast, the rate of the first reaction is independent of the presence of oxymyoglobin. The observed kinetics are in agreement with a reaction mechanism in which the nitric oxide that is initially bound to the Fe(II) centre of myoglobin is displaced by oxygen in a reversible ligand-exchange reaction prior to an irreversible electron transfer. The ligand-exchange process is dissociative in nature and depends bond breaking, and nitric oxide is suggested to be trapped in a protein cavity. The absorption spectrum of the intermediate, as resolved from the global analysis, is in agreement with a peroxynitrite complex, and the initial process must involve partial electron transfer.

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Electron Spin Resonance Analysis of Heme-Nitrosyl and Reduced Iron-Sulfur Centered Complexes in Allogeneic, Heterotopic Cardiac Transplants: Effects of Treatment with Pyrrolidine Dithiocarbamate

Cited by 17 publications

References 30 publications

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

Non-heme iron protein: A potential target of nitric oxide in acute cardiac allograft rejection

The complex role of iNOS in acutely rejecting cardiac transplants

Mechanism of Nitrosylmyoglobin Autoxidation: Temperature and Oxygen Pressure Effects on the Two Consecutive Reactions

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