The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: An in-depth analysis

Abstract

The underlying mechanism of the central nervous system (CNS) injury after acute carbon monoxide (CO) poisoning is interlaced with multiple factors including apoptosis, abnormal inflammatory responses, hypoxia, and ischemia/reperfusion-like problems. One of the current hypotheses with regard to the molecular mechanism of CO poisoning is the oxidative injury induced by reactive oxygen species, free radicals, and neuronal nitric oxide. Up to now, the relevant mechanism of this injury remains poorly understood. The weakening of antioxidant systems and the increase of lipid peroxidation in the CNS have been implicated, however. Accordingly, in this review, we will highlight the relationship between oxidative stress and CO poisoning from the perspective of forensic toxicology and molecular toxicology.     

Maternal nicotine exposure increases oxidative stress in the offspring

Fetal and neonatal nicotine exposure causes β-cell apoptosis and loss of β-cell mass, but the underlying mechanisms are unknown. The goal of this study was to determine whether maternally derived nicotine can act via the pancreatic nicotinic acetylcholine receptor (nAChR) during fetal and neonatal development to induce oxidative stress in the pancreas. Female Wistar rats were given saline or nicotine (1 mg/kg/day) via subcutaneous injection for 2 weeks prior to mating until weaning (postnatal day 21). In male offspring, nAChR subunit mRNA expression was characterized in the developing pancreas and various oxidative stress markers were measured at weaning following saline and nicotine exposure. The nAChR subunits 2-4, 6, 7, and β2–β4 were present in the pancreas during development. Fetal and neonatal exposure to nicotine significantly increased pancreatic GPx-1 and MnSOD protein expression, as well as islet ROS production. Furthermore, protein carbonyl formation was higher in nicotine-exposed offspring relative to controls, particularly within the mitochondrial fraction. There was also a nonsignificant trend toward higher serum 8-isoPG levels. These data suggest that β-cell apoptosis in the fetal and neonatal pancreas may be the result of a direct effect of nicotine via its receptor and that this effect may be mediated through increased oxidative stress.     

Brief exposure to carbon monoxide preconditions cardiomyogenic cells against apoptosis in ischemia-reperfusion

We examined whether and how pretreatment with carbon monoxide (CO) prevents apoptosis of cardioblastic H9c2 cells in ischemia-reperfusion. Reperfusion (6 h) following brief ischemia (10 min) induced cytochrome c release, activation of caspase-9 and caspase-3, and apoptotic nuclear condensation. Brief CO pretreatment (10 min) or a caspase-9 inhibitor (Z-LEHD-FMK) attenuated these apoptotic changes. Ischemia-reperfusion increased phosphorylation of Akt at Ser472/473/474, and this was enhanced by CO pretreatment. A specific Akt inhibitor (API-2) blunted the anti-apoptotic effects of CO in reperfusion. In normoxic cells, CO enhanced generation, which was inhibited by a mitochondrial complex III inhibitor (antimycin A) but not by a NADH oxidase inhibitor (apocynin). The CO-enhanced Akt phosphorylation was suppressed by an scavenger (Tiron), catalase or a superoxide dismutase (SOD) inhibitor (DETC). These results suggest that CO pretreatment induces mitochondrial generation of , which is then converted by SOD to H₂O₂, and subsequent Akt activation by H₂O₂ attenuates apoptosis in ischemia-reperfusion.     

Carbon monoxide exposure in rat heart: glutathione depletion is prevented by antioxidants

Rat hearts were perfused for 15min with buffer equilibrated with 0.01% or 0.05% CO. The buffer was equilibrated with 21% O(2) throughout. The ventricular glutathione content decreased by 76% and 84%, 90min post-exposure to 0.01% and 0.05% CO, respectively, compared with 0% CO controls (0.45+/-0.01 micromol/g wet tissue; +/-SEM, n=3). Both reduced and oxidised glutathione contributed to this decline. When ascorbate and Trolox C were included during exposure to 0.05% CO the glutathione pool was partly protected; here the glutathione decrease was 46%. In most hearts additional creatine kinase activity in the perfusate indicated minor tissue injury occurring immediately after the start and/or about 10min after the end of exposure to 0.01% CO or 0.05% CO. Ventricle lactate levels were unaffected by exposure to 0.01% CO. This evidence supports a role for oxidative stress in CO cardiotoxicity.     

Systemic oxidative stress in children and teenagers with Down syndrome

Aims

The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome.

Main methods

The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n = 20) compared to healthy controls (n = 18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically.

Key Findings

Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls.

Significance

The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.     

Carbon monoxide exposure in rat heart: evidence for two modes of toxicity

Rat hearts were perfused for 30 min with buffer equilibrated with CO. Mean data for hearts exposed to 0.01% CO show a 15% decrease in heart rate (HR) during exposure followed by recovery, with a further 17% decrease post exposure. Examination of time courses from individual perfusions shows that in 10 hearts exposed to 0.01% CO HR responded in different ways: no response (5 hearts); decrease during exposure followed by recovery (3 hearts); and decrease post exposure (2 hearts). There was a strong association between CO-induced HR decrease and release of creatine kinase into the perfusate, both of which were not prevented by the antioxidants, ascorbate, and Trolox C. Perfusate flow rate declined post exposure (4.9% and 8.9% with 0.01% and 0.05% CO, respectively) and this was prevented by antioxidants. CO may have two, independent, cardiotoxic effects; these may be mediated by CO-induced elevation of oxidant production, H2O2 in one case and peroxynitrite in the other.     

Metabolic consequences of the cytochrome c oxidase deficiency in brain of copper-deficient Mo(vbr) mice

Biochemical micromethods were used for the investigation of changes in mitochondrial oxidative phosphorylation associated with cytochrome c oxidase deficiency in brain cortex from Mo(vbr) (mottled viable brindled) mice, an animal model of Menkes' copper deficiency syndrome. Enzymatic analysis of cortex homogenates from Mo(vbr) mice showed an approximately twofold decrease in cytochrome c oxidase and a 1.4-fold decrease in NADH:cytochrome c reductase activities as compared with controls. Assessment of mitochondrial respiratory function was performed using digitonin-treated homogenates of the cortex, which exhibited the main characteristics of isolated brain mitochondria. Despite the substantial changes in respiratory chain enzyme activities, no significant differences were found in maximal pyruvate or succinate oxidation rates of brain cortex homogenates from Mo(vbr) and control mice. Inhibitor titrations were used to determine flux control coefficients of NADH:CoQ oxidoreductase and cytochrome c oxidase on the rate of mitochondrial respiration. Application of amobarbital to titrate the activity of NADH:CoQ oxidoreductase showed very similar flux control coefficients for control and mutant animals. Alternately, titration of respiration with azide revealed for Mo(vbr) mice significantly sharper inhibition curves than for controls, indicating a more than twofold elevated flux control coefficient of cytochrome c oxidase. Owing to the reserve capacity of respiratory chain enzymes, the reported changes in activities do not seem to affect whole-brain high-energy phosphates, as observed in a previous study using 31P NMR.     

The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance

The four gases, nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H₂S) and hydrogen cyanide (HCN) all readily inhibit oxygen consumption by mitochondrial cytochrome oxidase. This inhibition is responsible for much of their toxicity when they are applied externally to the body. However, recently these gases have all been implicated, to greater or lesser extents, in normal cellular signalling events. In this review we analyse the chemistry of this inhibition, comparing and contrasting mechanism and discussing physiological consequences. The inhibition by NO and CO is dependent on oxygen concentration, but that of HCN and H₂S is not. NO and H₂S are readily metabolised by oxidative processes within cytochrome oxidase. In these cases the enzyme may act as a physiological detoxifier of these gases. CO oxidation is much slower and unlikely to be as physiologically important. The evidence for normal physiological levels of these gases interacting with cytochrome oxidase is equivocal, in part because there is little robust data about their steady state concentrations. A reasonable case can be made for NO, and perhaps CO and H₂S, inhibiting cytochrome oxidase in vivo, but endogenous levels of HCN seem unlikely to be high enough.     

Benzo[a]pyrene, 3-methylcholanthrene and beta-naphthoflavone induce oxidative stress in hepatoma hepa 1c1c7 Cells by an AHR-dependent pathway

Polycyclic aromatic hydrocarbons have been shown to cause oxidative stress in vitro and in vivo in various animal models but the mechanisms by which these compounds produce oxidative stress are unknown. In the current study we have investigated the role of the aryl hydrocarbon receptor (AHR) in the production of reactive oxygen species (ROS) by its cognate ligands and the consequent effect on cyp1a1 activity, mRNA and protein expressions. For this purpose, Hepa 1c1c7 cells wild-type (WT) and C12 mutant cells, which are AHR-deficient, were incubated with increasing concentrations of the AHR-ligands, benzo[a]pyrene (B[a]P, 0.25-25 μM), 3-methylcholanthrene (3MC, 0.1-10 μM) and β-naphthoflavone (βNF, 1-50 μM). The studied AHR-ligands dose-dependently increased lipid peroxidation in WT but not in C12 cells. However, only B[a]P and βNF, at the highest concentrations tested, significantly increased H₂O₂ production in WT but not C12 cells. The increase in lipid peroxidation and H₂O₂ production by AHR-ligands were accompanied by a decrease in the cyp1a1 catalytic activity but not mRNA or protein expressions, which were significantly induced in a dose-dependent manner by all AHR-ligands, suggesting a post-translational mechanism is involved in the decrease of cyp1a1 activity. The AHR-ligand-mediated decrease in cyp1a1 activity was reversed by the antioxidant N-acetylcysteine. Our results show that the AHR-ligands induce oxidative stress by an AHR-dependent pathway.     

Modification of glycolysis affects cell sensitivity to apoptosis induced by oxidative stress and mediated by mitochondria

The effect of alteration of the glycolytic pathway on cell damage induced by oxidative stress was investigated with dihydrofolate reductase-deficient Chinese hamster ovary (CHO) cells that either overexpress cytosolic glycerol-3-phosphate dehydrogenase (CHO/cGPDH cells) or are depleted of the A subunit of lactate dehydrogenase as a result of anti-sense RNA expression (CHO/anti-LDH cells). The extent of oxidative phosphorylation in CHO/anti-LDH and CHO/cGPDH cells was increased and decreased, respectively, relative to that in parental CHO cells, as revealed by measurement of the intracellular content of ATP, the rate of cellular O(2) consumption, the mitochondrial membrane potential (DeltaPsi(m)), and the generation of reactive oxygen species. The sensitivity of these cell lines to cell death induced by the exogenous oxidant tert-butyl hydroperoxide decreased according to the rank order CHO/anti-LDH>CHO>CHO/cGPDH. Exogenous pyruvate markedly increased the sensitivity of CHO/cGPDH cells to oxidant-induced death. The differences among the three cell lines in susceptibility to oxidant-induced death were reflected in the proportion of oxidant-treated cells with a subdiploid DNA content, with a collapsed DeltaPsi(m), and with cytochrome c in the cytosol, indicating that death was mediated by apoptosis. These results demonstrate that the influx of respiratory substrate into mitochondria is an important determinant of cell sensitivity to oxidant-induced apoptosis.     

Mg2+- and ATP-dependent inhibition of transient receptor potential melastatin 7 by oxidative stress

Transient receptor potential melastatin 7 (TRPM7) is a Ca²⁺- and Mg²⁺-permeable nonselective cation channel that contains a unique carboxyl-terminal serine/threonine protein kinase domain. It has been reported that reactive oxygen species associated with hypoxia or ischemia activate TRPM7 current and then induce Ca²⁺ overload resulting in neuronal cell death in the brain. In this study, we aimed to investigate the molecular mechanisms of TRPM7 regulation by hydrogen peroxide (H₂O₂) using murine TRPM7 expressed in HEK293 cells. Using the whole-cell patch-clamp technique, it was revealed that the TRPM7 current was inhibited, not activated, by the application of H₂O₂ to the extracellular solution. This inhibition was not reversed after washout or treatment with dithiothreitol, suggesting irreversible oxidation of TRPM7 or its regulatory factors by H₂O₂ under whole-cell recording. Application of an electrophile, N-methylmaleimide (NMM), which covalently modifies cysteine residues in proteins, also inhibited TRPM7 current irreversibly. The effects of H₂O₂ and NMM were dependent on free [Mg²⁺]_i; the inhibition was stronger when cells were perfused with higher free [Mg²⁺]_i solutions via pipette. In addition, TRPM7 current was not inhibited by H₂O₂ when millimolar ATP was included in the intracellular solution, even in the presence of substantial free [Mg²⁺]_i, which is sufficient for TRPM7 inhibition by H₂O₂ in the absence of ATP. Moreover, a kinase-deficient mutant of TRPM7 (K1645R) was similarly inhibited by H₂O₂ just like the wild-type TRPM7 in a [Mg²⁺]_i- and [ATP]_i-dependent manner, indicating no involvement of the kinase activity of TRPM7. Thus, these data suggest that oxidative stress inhibits TRPM7 current under pathological conditions that accompany intracellular ATP depletion and free [Mg²⁺]_i elevation.     

The role of mitochondrial dehydrogenases in the generation of oxidative stress

In addition to complexes in the respiratory chain, few dehydrogenases playing key roles in the physiological metabolism in neurons, are able to generate reactive oxygen species (ROS) in mitochondria. One of them is the Krebs cycle enzyme, α-ketoglutarate dehydrogenase (α-KGDH), which is capable of producing superoxide and hydrogen peroxide by the E3 subunit of the enzyme regulated by changes in the NADH/NAD⁺ ratio. Mutations in the E3 subunit known to be related to diseases in humans were shown to have increased ROS-forming ability. α-Glycerophosphate dehydrogenase (α-GPDH) located on the outer surface of the inner membrane can also generate ROS, which is stimulated by Ca²⁺. ROS production by α-GPDH is unique as it does not require Ca²⁺ uptake and it is observed in respiring as well as damaged, bioenergetically incompetent mitochondria. The possible role of ROS generation by these dehydrogenases in brain pathology is discussed in this review.     

The effects of dietary restriction on oxidative stress in rodents

Oxidative stress is observed during aging and in numerous age-related diseases. Dietary restriction (DR) is a regimen that protects against disease and extends life span in multiple species. However, it is unknown how DR mediates its protective effects. One prominent and consistent effect of DR in a number of systems is the ability to reduce oxidative stress and damage. The purpose of this review is to comprehensively examine the hypothesis that dietary restriction reduces oxidative stress in rodents by decreasing reactive oxygen species (ROS) production and increasing antioxidant enzyme activity, leading to an overall reduction of oxidative damage to macromolecules. The literature reveals that the effects of DR on oxidative stress are complex and likely influenced by a variety of factors, including sex, species, tissue examined, types of ROS and antioxidant enzymes examined, and duration of DR. Here we present a comprehensive review of the existing literature on the effect of DR on mitochondrial ROS generation, antioxidant enzymes, and oxidative damage. In a majority of studies, dietary restriction had little effect on mitochondrial ROS production or antioxidant activity. On the other hand, DR decreased oxidative damage in the majority of cases. Although the effects of DR on endogenous antioxidants are mixed, we find that glutathione levels are the most likely antioxidant to be increased by dietary restriction, which supports the emerging redox-stress hypothesis of aging.     

In yeast redistribution of Sod1 to the mitochondrial intermembrane space provides protection against respiration derived oxidative stress

The antioxidative enzyme copper-zinc superoxide dismutase (Sod1) is an important cellular defence system against reactive oxygen species (ROS). While the majority of this enzyme is localized to the cytosol, about 1% of the cellular Sod1 is present in the intermembrane space (IMS) of mitochondria. These amounts of mitochondrial Sod1 are increased for certain Sod1 mutants that are linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). To date, only little is known about the physiological function of mitochondrial Sod1. Here, we use the model system Saccharomyces cerevisiae to generate cells in which Sod1 is exclusively localized to the IMS. We find that IMS-localized Sod1 can functionally substitute wild type Sod1 and that it even exceeds the protective capacity of wild type Sod1 under conditions of mitochondrial ROS stress. Moreover, we demonstrate that upon expression in yeast cells the common ALS-linked mutant Sod1^G93A becomes enriched in the mitochondrial fraction and provides an increased protection of cells from mitochondrial oxidative stress. Such an effect cannot be observed for the catalytically inactive mutant Sod1^G85R. Our observations suggest that the targeting of Sod1 to the mitochondrial IMS provides an increased protection against respiration-derived ROS.     

Regulation of heme oxygenase expression by alcohol, hypoxia and oxidative stress

AIM:To study the effect of both acute and chronic alcohol exposure on heme oxygenases(HOs) in the brain,liver and duodenum.METHODS:Wild-type C57BL/6 mice,heterozygous Sod2 knockout mice,which exhibit attenuated manganese superoxide dismutase activity,and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia.For acute alcohol exposure,ethanol was administered in the drinking water for 1 wk.Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies.HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.RESULTS:Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice.It did not alter liver HO-1 expression,nor HO-2 expression in the brain,liver or duodenum.In contrast,acute alcohol exposure decreased both liver HO-1 and HO-2 expression,and HO-2 expression in the duodenum of wild-type mice.The decrease in liver HO-1 expression was abolished in ARNT+/-mice.Sod2+/-mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression.However,alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2+/-mice.Collectively,these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner.Chronic alcohol exposure alters brain and duodenal,but not liver HO expression.However,acute alcohol exposure inhibits liver HO-1 and HO-2,and also duodenal HO-2 expression.CONCLUSION:The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.     

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Reactive oxygen species(ROS) are produced during normal physiologic processes with the consumption of oxygen. While ROS play signaling roles, when they are produced in excess beyond normal antioxidative capacity this can cause pathogenic damage to cells. The majority of such oxidation occurs in polyunsaturated fatty acids and sulfhydryl group in proteins, resulting in lipid peroxidation and protein misfolding, respectively. The accumulation of misfolded proteins in the endoplasmic reticulum(ER) is enhanced under conditions of oxidative stress and results in ER stress, which, together, leads to the malfunction of cellular homeostasis. Multiple types of defensive machinery are activated in unfolded protein response under ER stress to resolve this unfavorable situation. ER stress triggers the malfunction of protein secretion and is associated with a variety of pathogenic conditions including defective insulin secretion from pancreatic β-cells and accelerated lipid droplet formation in hepatocytes. Herein we use nonalcoholic fatty liver disease(NAFLD) as an illustration of such pathological liver conditions that result from ER stress in association with oxidative stress. Protecting the ER by eliminating excessive ROS viathe administration of antioxidants or by enhancing lipidmetabolizing capacity via the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.     

Persistence of hyperbaric oxygen-induced oxidative effects after exposure in rat brain cortex tissue

Hyperbaric oxygen (HBO) causes oxidative stress in several organs and tissues. Due to its high rate of blood flow and oxygen consumption, the brain is one of the most sensitive organs to this effect. Many studies have reported oxidative effects of HBO, but there is no comprehensive data about how long this effect persists. The aim of this study was to elucidate the duration of HBO-induced oxidative/antioxidant action. Male Sprague-Dawley rats were divided into 5 groups. Except for the controls, the animals were subjected to 100% oxygen for 2 h at 3 atm and differed from each other by the time to dissection after exposure that began at 30, 60, 90, or 120 min. Thiobarbituric acid-reactive substances (TBARS), as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity was determined in brain cortex tissue. Additionally, nitrite-nitrate (NO(x)) concentrations were measured. All measured parameters were found to be significantly increased 30 min after exposure. SOD and GSH-Px levels persisted at significantly high levels for 60 min. In conclusion, the oxidative effect of HBO was shown to persist only for 1 h. Further studies should be performed to elucidate the possible molecular interactions during this period.     

Responses to drought induced oxidative stress in five finger millet varieties differing in their geographical distribution

The study presents the impact of drought stress on five finger millet varieties (PR202, VL146, VL315, PES400 and VR708), representing contrasting areas of Indian sub-continent. Drought stress induced increase in the activity of superoxide dismutase, ascorbate peroxidase and glutathione reductase was higher in PR202 and VL315, while the activity was lower in the varieties PES400 and VR708. Ascorbate peroxidase : superoxide dismutase ratio, which is a crucial factor in alleviating drought stress, was higher in varieties PR202 and VL315, whilst the varieties PES400 and VR708 exhibited a lower ratio under stress. The variety PES400 recorded maximum stress induced damage, as indicated by higher accumulation of malondialdehyde and hydrogen peroxide; whereas the variety PR202 recorded least stress induced cytotoxic damage. The results clearly indicate that better drought tolerance of the variety PR202 is positively related to the capacity of its antioxidant system to scavenge reactive oxygen species, resulting in a reduced incidence of oxidative damage. Ascorbate peroxidase : superoxide dismutase ratio is found to be a critical factor governing the stress tolerance potential of different varieties. Therefore, varieties PR202 and VL315 were found to be tolerant while PES400 was susceptible to drought stress.     

氧化胁迫对酿酒酵母NAD(H)激酶突变体呼吸链活性的影响

【目的】了解酿酒酵母线粒体NAD(H)激酶Pos5p对呼吸链活性的维持是否与其抗氧化功能有关。【方法】比较在不同类型的氧化胁迫试剂作用下,野生菌BY4742、POS5基因缺失体pos5Δ及其回补体pos5Δ/POS5-YEp的呼吸链各个酶复合体的活性变化及细胞内活性氧水平变化。【结果】在非胁迫条件下,pos5Δ的各个复合体活性明显低于BY4742,而pos5Δ/POS5-YEp的活性有所恢复,这与它们的胞内活性氧水平相一致。在甲萘醌胁迫下,BY4742和pos5Δ的各个复合体活性都发生不同程度的下降,但pos5Δ/POS5-YEp的活性都升高。在H2O2、马来酸二乙酯胁迫下,除个别复合体外,BY4742、pos5Δ和pos5Δ/POS5-YEp的呼吸链复合体活性都降低,尤以pos5Δ的活性降低最为严重,BY4742的活性降低则较少,而pos5Δ/POS5-YEp在H2O2胁迫下的活性降低得到了缓解。说明甲萘醌、H2O2和马来酸二乙酯胁迫会造成酿酒酵母呼吸链各个复合体发生损伤,而过表达Pos5p则有助于缓解甲萘醌和H2O2引起的损伤。【结论】Pos5p对呼吸链的作用与其抗氧化功能有相关性。