Fatty acids as natural uncouplers preventing generation of O⋅−2 and H2O2 by mitochondria in the resting state

Korshunov, Sergey; Korkina, Olga V.; Ruuge, E. K.; Skulachev, Vladimir P.; Starkov, Anatoly A.

doi:10.1016/s0014-5793(98)01073-4

Cited by 181 publications

(120 citation statements)

References 25 publications

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“…In the PMA-stimulated NADPH system, it could cause dissociation of inhibitors of components of the NADPH complex, promote an ideal membrane environment for enzyme function, promote the phosphorylation or translocation of p47 phox (15,23,25), stimulate the NADPH oxidase proton pump (10,26), activate or promote PKC translocation (12,23,(27)(28)(29), stimulate the cell, mimicking, when in the micellar state, particulate stimuli (14,22), or stimulating the cell via the generation of eicosanoids (6). Regarding the mitochondrial-derived superoxide production, AA could act by its known mitochondrial uncoupling ability (carrying protons across the inner mitochondrial membrane), stimulating the opening of the permeability transition pore or acting as a prooxidant, and affecting electron transport (10,30,31). AA is a substrate for many components of the cytochrome P-450 complex, known to produce superoxide (7).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic acid triggers an oxidative burst in leukocytes

Pompéia

Cury-Boaventura

Curi

2003

Braz J Med Biol Res

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The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid-(AA) stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold), whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by Nethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

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Section: Discussionmentioning

confidence: 99%

Arachidonic acid triggers an oxidative burst in leukocytes

Pompéia

Cury-Boaventura

Curi

2003

Braz J Med Biol Res

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“…The heart has an abundant level of these proteins, particularly UCP2 (5). It has been postulated that the mild uncoupling ability of fatty acids is sufficient to maintain the mitochondrial membrane potential below a threshold level and prevent ROS formation by the respiratory chain (11). Differences in the uncoupling ability of oleate and palmitate have also been reported in model mitochondrial vesicles (22).…”

Section: Discussionmentioning

confidence: 99%

Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS

Hickson-Bick¹,

Sparagna²,

Buja³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The saturated fatty acid palmitate induces apoptosis in neonatal rat cardiomyocytes. This apoptosis is associated with early mitochondrial release of cytochrome c and a subsequent loss of mitochondrial membrane potential. Recent reports implicate a role for reactive oxygen species (ROS) in palmitate-induced apoptosis. We studied the role of ROS in palmitate-induced apoptosis in the neonatal rat cardiomyocyte and report no evidence of ROS involvement. ROS production, nitric oxide production, and nuclear factor-B activation were not increased above those observed using the nonapoptotic fatty acid oleate. Indeed, the production of ROS was significantly higher in cells treated with oleate. Furthermore, the presence of antioxidants and ROS scavengers did not attenuate the induction of apoptosis by palmitate. Variations in the fatty acid-to-albumin ratio from 2:1 to 7:1 had no effect on the absence of ROS production or on the extent of apoptosis. No evidence was found for an increase in oxidative protein modification in palmitate-treated cells. Our results lead us to conclude that oxidative stress does not play a role in palmitate-induced apoptosis.antioxidants; nitric oxide; mitochondria; nuclear factor-B

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“…(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) at Complex I (by a yet unresolved mechanism, O 2 . is released to the matrix) (2) and via autooxidation of the ubisemiquinone anion radical at Complex III (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), where O 2 . could be released into both sides of the membrane (2).…”

mentioning

confidence: 99%

“…FAOOH may also decompose to toxic epoxy acids and ␣,␤,␥,␦-unsaturated aldehydes (18). It has been found that even a slight increase of H ϩ backflux into the matrix may substantially suppress mitochondrial ROS formation (7)(8)(9)(10)(11) synthesis also suppresses ROS formation (7)(8)(9); therefore most ROS are produced in the non-phosphorylating state. This effect of uncoupling or ATP synthesis is due to increased respiration and hence concomitantly shortened lifetime of UQ .…”

mentioning

confidence: 99%

Hydroperoxy Fatty Acid Cycling Mediated by Mitochondrial Uncoupling Protein UCP2

Jabůrek

Miyamoto

Mascio

et al. 2004

Journal of Biological Chemistry

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Using Escherichia coli-expressed UCP2 reconstituted into liposomes we found that LAOOH induced purine nucleotide-sensitive H ؉ uniport in UCP2-proteoliposomes with higher affinity than LA (K m values 97 M for LAOOH and 275 M for LA). In UCP2-proteoliposomes LAOOH also induced purine nucleotide-sensitive K ؉ influx balanced by anionic charge transfer, indicating that LAOOH was also transported as an anion with higher affinity than linoleate anion, the K m values being 90 and 350 M, respectively. These data suggest that hydroperoxy fatty acids are transported via UCP2 by a fatty acid cycling mechanism. This may alternatively explain the observed activation of UCP2 by the externally generated superoxide. The ability of LAOOH to induce UCP2-mediated H ؉ uniport points to the essential role of superoxide reaction products, such as hydroperoxyl radical, hydroxyl radical, or peroxynitrite, initiating lipoperoxidation, the released products of which support the UCP2-mediated uncoupling and promote the feedback down-regulation of mitochondrial reactive oxygen species production.

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Fatty acids as natural uncouplers preventing generation of O^⋅−₂ and H₂O₂ by mitochondria in the resting state

Cited by 181 publications

References 25 publications

Arachidonic acid triggers an oxidative burst in leukocytes

Arachidonic acid triggers an oxidative burst in leukocytes

Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS

Hydroperoxy Fatty Acid Cycling Mediated by Mitochondrial Uncoupling Protein UCP2

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