Nitric Oxide and Cytochrome c Oxidase: Mechanisms of Inhibition and NO Degradation

Sarti, Paolo; Giuffrè, Alessandro; Forte, Elena; Mastronicola, Daniela; Barone, Maria Cecilia; Brunori, Maurizio

doi:10.1006/bbrc.2000.3117

Cited by 152 publications

(133 citation statements)

References 25 publications

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“…6, A or B. Hence, the reduction potential of the PTIO/PTIO ϩ and C-PTIO/C-PTIO ϩ couples is the same and was calculated using K 8 and E o ( ⅐ NO 2 /NO 2 -) ϭ 1.04 V to be 912 mV. The latter value is in agreement with the mid-potentials, which were determined by cyclic voltammetry to be 915 Ϯ 10 and 936 Ϯ 21 mV, respectively.…”

Section: Methodssupporting

confidence: 69%

“…However, high steadystate levels of ⅐ NO function critically in modulating inflammatory, infectious, and degenerative diseases (2)(3)(4)(5)(6). The reaction of ⅐ NO with metalloproteins can abrogate the function of proteins (7,8). Moreover, the reactions of ⅐ NO with oxygen and superoxide convert ⅐ NO into other reactive nitrogen species such as ONOO Ϫ , ⅐ NO 2 , or N 2 O 3 , which can react with virtually all of the classes of biomolecules including amino acids, lipids, DNA, thiols, and metals (5, 6, 9 -11).…”

Section: Ptiosmentioning

confidence: 99%

See 1 more Smart Citation

Reactions of PTIO and Carboxy-PTIO with ·NO, ·NO2, andO2.¯

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

181

124

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Nitronyl nitroxides, such as derivatives of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIOs), react with ⅐ NO to form the corresponding imino nitroxides (PTIs) and ⅐ NO 2 . PTIOs are considered as monitors of ⅐ NO, stoichiometric sources of ⅐ NO 2 , biochemical and physiological effectors, specific tools for the elimination of ⅐ NO, and potential therapeutic agents. However, a better understanding of the chemical properties of PTIOs, especially following their reaction with ⅐ NO, is necessary to resolve many of the reported discrepancies surrounding the effects of PTIOs and to better characterize their potential therapeutic activity. We have generated electrochemically the oxidized and reduced forms of PTIO and carboxy-PTIO (C-PTIO), characterized their absorption spectra, and determined the reduction potentials for the oxoammonium/nitroxide and nitroxide/hydroxylamine couples. The rate constants for the reaction of ⅐ NO 2 with PTIO and C-PTIO to form the corresponding oxoammonium cations (PTIO ؉ s) and nitrite were determined to be (1. Nitric oxide ( ⅐ NO) 1 is synthesized by ⅐ NO synthase from the substrate L-arginine in a wide variety of cell types and is a major participant in numerous beneficial physiological functions such as blood pressure regulation, inhibition of platelet aggregation, and neurotransmission (1). However, high steadystate levels of ⅐ NO function critically in modulating inflammatory, infectious, and degenerative diseases (2-6). The reaction of ⅐ NO with metalloproteins can abrogate the function of proteins (7, 8). Moreover, the reactions of ⅐ NO with oxygen and superoxide convert ⅐ NO into other reactive nitrogen species such as ONOO Ϫ , ⅐ NO 2 , or N 2 O 3 , which can react with virtually all of the classes of biomolecules including amino acids, lipids, DNA, thiols, and metals (5, 6, 9 -11). One therapeutic approach to ameliorate ⅐ NO-induced biological damage is to use ⅐ NO scavengers, preferably selective scavengers that distinguish between free ⅐ NO and species exhibiting ⅐ NO-like biological activity.The use of nitronyl nitroxides, such as 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), as selective traps for ⅐ NO is rapidly increasing as reflected by the numerous publications in the recent biomedical literature. PTIO and its derivatives were shown to react with ⅐ NO to form the corresponding imino nitroxides and ⅐ NO 2 (12-16), where k 1 ϭ (0.5 Ϫ 16) ϫ 10 4 M Ϫ1 s Ϫ1 (Reaction 1) (12, 14, 16).Both the nitronyl nitroxide and the imino nitroxide are detectable and distinguishable by EPR spectroscopy, and various PTIOs are used as spin traps for ⅐ NO (13, 14, 16 -18). In addition, Akaike et al. (12) demonstrated that excess of ⅐ NO 2 had no effect on the EPR spectrum of PTIOs and, subsequently, Reaction 1 has been adopted to generate ⅐ NO 2 (19,20). Likewise, direct scavenging of ⅐ NO by PTIOs has been shown to inhibit endothelium-derived relaxing factor (EDRF) in bioassay in vitro (12), to cause cell cycle alteration, to result in oxidative stress and a...

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Section: Methodssupporting

confidence: 69%

Section: Ptiosmentioning

confidence: 99%

Reactions of PTIO and Carboxy-PTIO with ·NO, ·NO2, andO2.¯

Goldstein

Russo

Samuni

2003

Journal of Biological Chemistry

181

124

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“…Unlike the Cco oxidase reaction, which requires four electrons, the Cco NO 2 Ϫ reductase reaction involves a one-electron transfer. Although the precise mechanism of the NO 2 Ϫ reduction in Cco remains to be determined, it is useful to note that a NO 2 Ϫ -ferric a 3 complex has been observed in studies aimed at examining the interaction between NO and Cco (53)(54)(55)(56). Moreover, it has been reported that a heme-nitrosyl complex is formed at the binuclear reaction center in bovine heart Cco when incubated in the presence of excess NO 2 Ϫ and reductant (57).…”

Section: Discussionmentioning

confidence: 99%

Oxygen-regulated isoforms of cytochrome c oxidase have differential effects on its nitric oxide production and on hypoxic signaling

Castello

Woo

Ball

et al. 2008

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

102

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Recently, it has been reported that mitochondria possess a novel pathway for nitric oxide (NO) synthesis. This pathway is induced when cells experience hypoxia, is nitrite (NO 2 ؊ )-dependent, is independent of NO synthases, and is catalyzed by cytochrome c oxidase (Cco). It has been proposed that this mitochondrially produced NO is a component of hypoxic signaling and the induction of nuclear hypoxic genes. In this study, we examine the NO 2 ؊ -dependent NO production in yeast engineered to contain alternative isoforms, Va or Vb, of Cco subunit V. Previous studies have shown that these isoforms have differential effects on oxygen reduction by Cco, and that their genes (COX5a and COX5b, respectively) are inversely regulated by oxygen. Here, we find that the Vb isozyme has a higher turnover rate for NO production than the Va isozyme and that the Vb isozyme produces NO at much higher oxygen concentrations than the Va isozyme. We have also found that the hypoxic genes CYC7 and OLE1 are induced to higher levels in a strain carrying the Vb isozyme than in a strain carrying the Va isozyme. Together, these results demonstrate that the subunit V isoforms have differential effects on NO 2 ؊ -dependent NO production by Cco and provide further support for a role of Cco in hypoxic signaling. These findings also suggest a positive feedback mechanism in which mitochondrially produced NO induces expression of COX5b, whose protein product then functions to enhance the ability of Cco to produce NO in hypoxic/anoxic cells.hypoxia ͉ mitochondria ͉ reactive oxygen species ͉ nitrite ͉ yeast I t has been known for quite some time that the mitochondrial respiratory chain is capable of generating reactive oxygen species (ROS) that account for much of the oxidative stress experienced by cells (1-3). The levels of these ROS increase when electron flow through the respiratory chain is inhibited by respiratory inhibitors (4-6) or altered by uncoupling electron transport from oxidative phosphorylation (7,8). Several studies have shown that exposure of cells and tissues to hypoxia increases ROS levels and oxidative stress (9-11). This increase in oxidative stress during exposure to hypoxia depends on a functional mitochondrial respiratory chain (10). It is currently unclear whether this increase is the result of increased generation or decreased destruction of ROS under hypoxic conditions. In yeast cells, the increase in ROS levels and oxidative stress is transient, as determined by shifting cells from normoxia to anoxia (10). During this shift, cells experience a continuum of decreasing oxygen concentrations and a transient increase in the levels of carbonylation of both mitochondrial and cytosolic protein, an increase in 8-OH-dG levels in mtDNA, and an increase in expression of the SOD1 gene. Many of the proteins that are carbonylated during a shift from normoxia to anoxia are the same proteins that are carbonylated when cells are exposed to menadione, a redox recycling agent that produces elevated intracellular levels of superoxide (12). ...

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“…NO inhibits by reacting with either the reduced or oxidised binuclear (oxygen-binding ) site of cytochrome oxidase to give either cytochrome a 3 2C -NO or cytochrome a 3 3C -NO 2 ¡ (18)(19)(20). Endogenously produced NO may tonically inhibit respiration at cytochrome oxidase in some cells (21,22). Inhibition is in competition with oxygen, so that NO can dramatically increase the apparent K m of respiration for oxygen (2,(12)(13)(14).…”

Section: No Actions On Mitochondriamentioning

confidence: 99%