The effect of hyperoxia on superoxide production by lung submitochondrial particles

Turrens, Julio F.; Freeman, Bruce Α.; Levitt, Jennifer G.; Crapo, James D.

doi:10.1016/0003-9861(82)90518-5

Cited by 405 publications

(174 citation statements)

References 30 publications

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“…Even if shear-induced NO production remained the same at 21% vs. 5% O 2 (according to Fig. 6A, it is increased at 21% O 2 ), O 2 ⅐ Ϫ formation by the ETC is known to increase linearly with PO 2 (42,74) and, since O 2 ⅐ Ϫ does not diffuse across cell membranes, the fraction of shear-induced NO that forms ONOO Ϫ intramitochondrially would be expected to be higher at 21% vs. 5% O 2 .…”

Section: Discussionmentioning

confidence: 94%

“…Since it is known that 1-4% of O 2 reacting with the ETC is incompletely reduced to O 2 ⅐ Ϫ , and the O 2 ⅐ Ϫ formation rate by the ETC complexes III and I increases linearly with O 2 concentration (42,74), we hypothesized that, under flow, the relative "hyperoxic state" of 21% O 2 raises the O 2 concentration in EC mitochondria and enhances the formation of O 2 ⅐ Ϫ , which, via the reaction with shear-induced NO, increases the intramitochondrial ONOO Ϫ levels and potentiates the inhibition of respiration. Although it is known that 1) either hyperoxia (21-100% O 2 ) or H (1-3% O 2 )/RO (21% O 2 ) increases the mitochondrial O 2 ⅐ Ϫ generation and inhibits respiration (9,21,33,67,71) and 2) shear at 21% O 2 increases the EC ONOO Ϫ formation intramitochondrially (30), the respiratory function of sheared ECs at 21% O 2 and at lower, but physiological, O 2 levels has not been examined.…”

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confidence: 99%

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Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Jones¹,

Han²,

Presley³

et al. 2008

American Journal of Physiology-Cell Physiology

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Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO Ϫ ) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O2, compared with more physiological O2 tensions (PO2), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O2 ⅐ Ϫ ) generation leading to ONOO Ϫ formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2 consumption rates of bovine aortic ECs sheared (10 dyn/cm 2 , 30 min) at 5%, 10%, or 21% O2 or left static at 5% or 21% O2. Respiration was inhibited to a greater extent when ECs were sheared at 21% O2 than at lower PO2 or left static at different PO2. Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO Ϫ scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O2 ⅐ Ϫ production was higher in ECs sheared at 21% than at 5% O2, as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O2 was modestly increased compared with ECs sheared at lower PO2, suggesting that eNOS activity may be higher at 21% O2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2 ⅐ Ϫ production, leads to enhanced ONOO Ϫ formation intramitochondrially and suppression of respiration. shear stress; endothelium; mitochondria; reactive oxygen species MITOCHONDRIA ARE THE SUBCELLULAR organelles for the production of cellular energy, but they also activate intracellular signaling pathways that modulate cell proliferation or promote cell cycle arrest and apoptosis by oxidative or nitrosative reactions. These reactions are regulated by the matrix concentration of nitric oxide (NO), which diffuses to the mitochondria from the cytosolic NO synthase (NOS) isoforms and is thought to be produced also locally by a mitochondrial NOS variant (11). In rat heart, skeletal muscle and liver mitochondria (15,57,58), isolated rat hearts (59), and whole animals (68), NO at physiological concentrations binds reversibly and in competition with oxygen (O 2 ) to the reduced binuclear center Cu B /a 3 of cytochrome-c oxidase (complex IV) of the electron transport chain (ETC) and inhibits mitochondrial O 2 uptake. At slightly higher concentrations, NO oxidizes ubiquinol of ubiquinolcytochrome c reductase (complex III) to increase unstable ubisemiquinone, which, by univalent electron transfer to O 2 , produces the reactive O 2 species (ROS) superoxide (O 2 ⅐ Ϫ ) (57, 58). O 2 ⅐ Ϫ generated from that location is released both into the matrix and intermembrane space (51), where it is dismutated to hydrogen peroxide (H 2 O 2 ) by manganese superoxide dismutase (MnSOD) and copper zinc SOD (CuZ...

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Jones¹,

Han²,

Presley³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…Thus, for all measurements of intracellular oxidative stress, [64][65][66] cells were allowed to incubate in suspension culture for 24 h before analysis. To detect intracellular ROS, SMG cells were treated with 5 mM CellRox and 2 mM Calcein AM (Life Technologies) for 30 min, washed with 5 mL DPBS, and resuspended at a concentration of 4.0 · 10 6 cells/ mL in 50 mL/well aliquots in black 96-well plates.…”

Section: Cell Culturementioning

confidence: 99%

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Shubin

Felong

Graunke

et al. 2015

Tissue Engineering Part A

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More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications.

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“…Finally, in a test of resistance to experimental oxidative stress, flies aged 9-10 days were exposed to hyperoxia (100% oxygen), which accelerates the production of superoxide anion radicals (28), the substrate for SOD. If the Sod A4V -1; Sod x16/x39 and Sod G41D -1; Sod x16/x39 animals were approaching a threshold of impaired physiological performance in this age range, due to diminished SOD activity, then this oxidative challenge should expose their latent weakness, resulting in decreased survival times.…”

Section: Fals Sod Expression Confers Incomplete Rescue Of Life Spanmentioning

confidence: 99%

Phenotypic effects of familial amyotrophic lateral sclerosis mutant Sod alleles in transgenic Drosophila

Mockett

Radyuk

Benes

et al. 2002

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

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A subset of patients suffering from familial amyotrophic lateral sclerosis (FALS) exhibit point mutations in the gene encoding Cu-Zn superoxide dismutase [superoxide:superoxide oxidoreductase, EC 1.15.1.1 (SOD)]. The human wild-type and five FALS Sod mutant transgenes were introduced into the fruit fly, Drosophila melanogaster, in a Cu-Zn Sod null background. Sod null flies had dramatically decreased life span, glutathione and methionine content, fertility, locomotor activity, and resistance to hyperoxic stress, compared with wild-type controls. All of these phenotypic manifestations were rescued fully by a single human wild-type allele, expressing 5-10% of wild-type SOD activity. Full recovery of wild-type life span was also observed when human mutant and wild-type alleles were placed together in the fly Sod null background. The FALS Sod mutations alone caused a recessive phenotype, usually involving low or undetectable levels of SOD activity, in which: (i) full restoration of the wild-type phenotype was observed among young adults, and (ii) older adults exhibited a sudden increase in oxidative stress, accompanied by physiological impairment of abrupt onset, and followed by premature death. Thus, the minimal SOD activity associated with the FALS Sod mutations appears to determine longevity, not by chronically increasing oxidative stress, but by limiting the time in which a viable redox environment can be maintained. However, the dominant gain of function by mutant SOD, which occurs in human patients and in the transgenic mouse model of FALS, is not observed in Drosophila.

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The effect of hyperoxia on superoxide production by lung submitochondrial particles

Cited by 405 publications

References 30 publications

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Development of Poly(Ethylene Glycol) Hydrogels for Salivary Gland Tissue Engineering Applications

Phenotypic effects of familial amyotrophic lateral sclerosis mutant Sod alleles in transgenic Drosophila

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