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At least 163 records · Page 9Linked to original sources
PubMed1999

Hyperoxia inhibits proliferation of Mv1Lu epithelial cells independent of TGF-beta signaling.

High concentrations of O(2) inhibit epithelial cell proliferation that resumes on recovery in room air. To determine whether growth arrest is mediated by transforming growth factor-beta (TGF-beta), changes in cell proliferation during exposure to hyperoxia were assessed in the mink lung epithelial cell line Mv1Lu and the clonal variant R1B, which is deficient for the type I TGF-beta receptor. Mv1Lu cells treated with TGF-beta accumulated in the G(1) phase of the cell cycle as determined by propidium iodide staining, whereas proliferation of R1B cells was unaffected by TGF-beta. In contrast, hyperoxia inhibited proliferation of both cell lines within 24 h of exposure through an accumulation in the S phase. Mv1Lu cells treated with TGF-beta and exposed to hyperoxia accumulated in the G(1) phase, suggesting that TGF-beta can inhibit the S phase accumulation observed with hyperoxia alone. Cyclin A was detected in cultures exposed to room air or growth arrested by hyperoxia while decreasing in cells growth arrested in the G(1) phase by TGF-beta. Finally, hyperoxia failed to activate a TGF-beta-dependent transcriptional reporter in both Mv1Lu and R1B cells. These findings reveal that simple growth arrest by hyperoxia involves a defect in S phase progression that is independent of TGF-beta signaling.

Adenocarcinoma↗
PubMed1985

Mechanism of hyperoxia-induced pulmonary vascular paralysis: effect of antioxidant pretreatment.

We designed experiments using isolated rabbit lungs to determine the effect of hyperoxia on the pulmonary vasoconstriction caused by the infusion of the lipid peroxide tert-butyl hydroperoxide (t-bu-OOH), which produces vasoconstriction by stimulating the pulmonary synthesis of thromboxane. Exposure to 48-60 h of 100% O2 at 1 ATA markedly reduced the increase in pulmonary artery pressure caused by t-bu-OOH infusion. We also investigated whether the mechanism for the attenuated vasoconstriction was due to altered production of arachidonate mediators or oxidant-induced damage to the contractile mechanism. In addition to infusing t-bu-OOH, which selectively stimulates thromboxane production, we also infused Intralipid, an esterified fatty acid emulsion that stimulates production of both thromboxane and prostacyclin. These experiments were done to study the effect of hyperoxia on prostacyclin synthesis. To determine if antioxidant therapy would prevent the changes in mediator production and vascular reactivity caused by hyperoxia, we pretreated animals with the antioxidants butylated hydroxyanisole (BHA) or vitamin E. The lack of vascular reactivity to t-bu-OOH was not due to a decrease in thromboxane synthesis or an increase in prostacyclin synthesis. Hyperoxia did not affect thromboxane synthesis during basal conditions or after stimulation of synthesis by t-bu-OOH. 100% O2 also did not effect the basal synthesis of prostacyclin by the lung. Hyperoxia did, however, markedly reduce prostacyclin synthesis when it was stimulated by Intralipid infusion. Antioxidant pretreatment did not reverse the inhibition of prostacyclin synthesis but did prevent the loss of vascular reactivity caused by hyperoxia. Thus hyperoxia causes vascular paralysis through oxidant-induced injury to the pulmonary vasculature.

Animals↗
PubMed1989

Polyamines, DNA synthesis, and tolerance to hyperoxia of mice and rats.

Adaptation to hyperoxia has been attributed to increased activities of protective enzymes, but we suggest that an additional factor may be the lung's capacity to repair itself in hyperoxia. Such repair would require increased polyamines, but there are reports that two key enzymes of polyamine metabolism are suppressed by hyperoxia or oxidants. Because rats can adapt to hyperoxia but mice cannot, we compared their changes of polyamine metabolism and judged cell repair by using [3H]thymidine to estimate DNA synthesis. Both species developed increased ornithine decarboxylase activity and putrescine content, but the mouse did not develop increased S-adenosylmethionine decarboxylase activities or increases of spermidine and spermine as did the rat when exposed to 85% O2. Furthermore, we confirmed that the rat lung does respond to hyperoxia with increased DNA synthesis, but the mouse lung does not. The results suggest that in addition to increased activities of protective enzymes, increased repair processes in the rat lung may play a role in its capacity to adapt to hyperoxia. The incomplete response of polyamine metabolism in mice may contribute to their inability to adapt in hyperoxia.

Adaptation, Physiological↗
PubMed1994

Neonatal hyperoxia and cytochrome P450 imprinting in adulthood.

We hypothesized that during a critical neonatal period hyperoxia may produce alterations of sex-specific cytochrome P450 isozymes in adulthood (enzyme imprinting). To test this, newborn rats were exposed to 24 or 72 h of hyperoxia (O2 > 95%) within 24 h after birth and killed at 120 d. In males, significant negative imprinting (decrease) was found in total cytochrome P450 content and male-specific CYP2C11 in the hyperoxia groups. Positive imprinting (increase) was noted in CYP1A2 and male-specific CYP3A2 in the 72-h hyperoxia group. These alterations were essentially similar when expressed on a per microsomal protein or per liver basis. In addition, the level of hepatic glucocorticoid receptor in adult male rats was elevated after neonatal hyperoxia. In females, there was a significant body and liver weight loss after hyperoxic exposure, which resulted in a negative imprinting of CYP1A2 and female-specific 2C12 in the 72-h hyperoxia group on a per liver basis, whereas the measured parameters were unaltered when expressed per microsome. In general, the changes were more marked with longer hyperoxic exposure, suggesting that more pronounced alterations may be induced with prolonged neonatal hyperoxia. Because hyperoxic exposure in premature neonates is a common clinical practice and decreased CYP2C11 in adult males is expected to result in feminization, we believe that the scope of this work should be expanded and eventually tested for its relevance in human subjects.

Animals↗
PubMed1996

Effects of hypoxia and hyperoxia on oxygen-transfer properties of the blood of a viviparous snake

Red cell oxygen affinity, red cell nucleoside triphosphate (NTP) levels and blood oxygen-carrying capacity were determined for male, nonpregnant and pregnant female, and fetal garter snakes Thamnophis elegans exposed to hypoxia (5 % oxygen) and hyperoxia (100 % oxygen). Male and nonpregnant female snakes were maintained under these conditions for up to 3 weeks and exhibited an apparent maximal change in oxygen affinity after 14 days of hypoxia and hyperoxia. Red cell NTP levels decreased and oxygen affinity increased with exposure to hypoxia, while exposure to hyperoxia promoted an increase in red cell NTP concentrations and a decrease in red cell oxygen affinity in the males. Hyperoxia-exposed nonpregnant females did not show a significant change in oxygen affinity. After 14 days of hypoxia, the pregnant females showed an increase in red cell oxygen affinity which was associated with a decrease in red cell NTP concentration and in the molar ratio of NTP/hemoglobin relative to normoxic controls. Fourteen days of hyperoxia did not result in a change in oxygen affinity of red cells from the pregnant female, but did promote a slight increase red cell NTP concentrations. The blood parameters of fetuses from females exposed to hypoxia or hyperoxia did not differ from those of normoxic control fetuses. The fetuses of females exposed to hypoxia suffered greater mortality, appeared less developed and had a lower average wet mass than the fetuses of normoxic- and hyperoxic-exposed females. Neither hypoxia nor hyperoxia altered the oxygen-carrying capacity of the blood in any group of snake.

Journal Article↗
PubMed1987

Effect of hypoxia and hyperoxia on cardiorespiratory responses during exercise in man.

To clarify the role of the carotid body in the mechanism governing exercise hyperpnea, the effect of hypoxia and hyperoxia on ventilation and cardiac output was studied in four healthy men. The VE increased 10.7% in hypoxia and decreased 10.1% in hyperoxia from normoxia as judged from the steady-state values during exercise. On the contrary, Q showed only a slight reduction of -3.2% in hyperoxia. The hypoxic hyperpnea and hyperoxic hypopnea led to a concomitant alteration in PETCO2. An overshoot following the onset of exercise was observed during the first 30s of VE response in hypoxia, which damped progressively in normoxia and hyperoxia. No remarkable difference was observed in the early transient responses of Q between hypoxia and hyperoxia. The discrepancy in the dynamics between VE and Q led to a phasic deviation in PETCO2; an isocapnic transition from the control to stimulus period in normoxia, hypocapnic in hypoxia and hypercapnic in hyperoxia. The time constant representing the kinetics of VE and that for VCO2 prolonged significantly in hyperoxia. These results support the cardiodynamic consequence of exercise hyperpnea, i.e., the carotid body is the first to respond to the increase in CO2 flow into the lungs.

Adult↗
PubMedDate not supplied

Hydrogen peroxide release from alveolar macrophages and alveolar type II cells during adaptation to hyperoxia in vivo.

The effect of hyperoxia (1-14 days, 85% O2) on rat alveolar macrophage and alveolar type II cell oxidant and antioxidant characteristics was investigated. Unstimulated control macrophages (2 h ex vivo) released hydrogen peroxide at a rate of 3.5 +/- 1.3 nmol/min mg protein-1, which was a cyanide-sensitive process. H2O2 release from alveolar macrophages decreased slightly but not significantly after 1 day in hyperoxia and increased significantly after 3 days (180%, p less than .05) and 14 days (380%, p less than .01). When H2O2 release was expressed as nmol from total macrophages per animal, the increase after 14 days in hyperoxia was 760%. H2O2 generation by hyperoxic macrophages was cyanide resistant, indicating the involvement of active NADPH oxidase. In both control and hyperoxic macrophages H2O2 release could be significantly stimulated with phorbol myristate acetate (PMA). Comparisons of H2O2 release by freshly isolated alveolar macrophages and alveolar type II cells must be cautiously interpreted because some cell functions may change during the isolation procedure. Freshly isolated (6 h ex vivo) control alveolar type II cells were found to generate H2O2 at a rate of 0.26 +/- 0.05 nmol/min mg protein-1. In type II cells H2O2 release, calculated as nmol/mg protein, decreased during the first 7 days of hyperoxia to 10% (p less than .01) of the control value and then returned back up to the control level after 14 days. A similar decrease was observed if H2O2 release was calculated as nmol/cell number. H2O2 release from control and hyperoxic type II cells was cyanide sensitive. The decrease in H2O2 release in type II cells was associated with cell membrane injury (as assessed by electron microscopy), while biochemical markers of cellular injury (trypan blue exclusion and cellular high-energy phosphates ATP, ADP) were unchanged. The ability of type II cells to scavenge extracellular H2O2 did not change in acute hyperoxia, but it increased significantly during the second week in hyperoxia. These results indicate that macrophages but not type II cells are stimulated to produce H2O2 during prolonged exposure to hyperoxia.

Adaptation, Physiological↗
PubMedDate not supplied

In vitro effects of hyperoxia on alveolar type II pneumocytes: inhibition of glutathione synthesis increases hyperoxic cell injury.

An in vitro model of alveolar epithelial oxidant injury was developed based on exposure to hyperoxia of cultured guinea pig type II pneumocytes using a biphasic cell culture system in aerobiosis. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in providing protection against hyperoxia. A 2-day type II cell culture in normoxia was associated with a significant decrease in protein, catalase, and Cu-Zn SOD cell content, whereas ATP cell content, Mn-SOD, and glutathione peroxidase (GPx) activities did not change and glutathione cell content significantly increased. Exposure of type II cells to hyperoxia did not induce significant changes in cell content in protein, SOD, catalase, GPx, or glutathione cell content when compared to control cells (exposed to normoxia). With ATP cell content expressed as a cell injury index (CII), type II cell injury was found to increase with increasing O2 concentrations. Indeed, a 2-day 50% O2 and 95% O2 exposure resulted in a CII of -7.5 +/- 6.2% and 17.9 +/- 5.9%, respectively, LDH release by type II cells was not significantly increased after hypoxic exposure. Cell injury effects of hyperoxia did not correlate with the endogenous antioxidant enzyme activities (SOD, Mn-SOD, catalase). In marked contrast, there was a significant correlation between the CII and total glutathione content of type II cells (p < .01). This correlation was largely due to the close relationship between CII and reduced glutathione. Hyperoxic induced cell injury (as demonstrated by CII > 0) was clearly associated with significantly lower intracellular glutathione level when compared to experiments without hyperoxia induced cell injury (CII < 0). In addition, in the presence of buthionine sulfoximine (BSO), the ability of type II cells to synthetize new glutathione was severely impaired, whereas ATP cell content and cell antioxidant enzyme activities did not change. As a consequence, the reduction of intracellular glutathione significantly increased the susceptibility of cells to hyperoxia injury (p < .05). The results strongly support the hypothesis that the regulation of glutathione levels is an important mechanism in protecting hyperoxia-induced type II cell injury.

Aerobiosis↗
PubMed1990

Endotoxin extends survival of adult mice in hyperoxia.

Research on endotoxin protection from oxygen toxicity is presently limited to the rat model since only rats have been protected by endotoxin. This study reports that endotoxin also extends survival of adult male mice in hyperoxia (greater than 99% oxygen at 1 ATA). Initially, 4-month-old male mice were treated with Boivin-extracted E. coli endotoxin and placed in hyperoxia. Zymosan-primed mice receiving 2 or 10 micrograms endotoxin, and unprimed mice receiving 10-40 micrograms endotoxin, showed moderate protection against hyperoxia; 11/15 Boivin-treated mice survived 120 hours exposure to hyperoxia with time-of-death in hyperoxia = 126.7 +/- 4.4 hours (mean +/- SEM, n = 15). This contrasts with untreated male mice; 0/4 survived 120 hours exposure to hyperoxia with mean survival = 103.5 +/- 3.5 hours. Mice receiving 20 or 60 micrograms Westphal-extracted endotoxin were not protected nor were older female mice receiving 20 micrograms Boivin-extracted endotoxin. This study suggests that age, sex, the extraction method used to obtain endotoxin, and possibly the time of year when endotoxin is administered, are important variables in allowing endotoxin to extend survival of mice in hyperoxia.

Analysis of Variance↗
PubMed1992

Effects of endurance training under hyperoxia on serum and tissue lipid levels in rats.

Effects of 6 weeks endurance training (5 days per week) under hyperoxia (60% O2 plus 40% N2) on serum and tissue lipid levels were investigated in male rats. Rats were divided into 4 groups: normoxia-control (NC), hyperoxia-control (HC), normoxia-training (NT), and hyperoxia-training (HT). NT and HT groups were run on a treadmill in a chamber at 20 m per min with a 6 degree gradient for 30 min. The chamber was perfused with hyperoxic gas. After training under hyperoxia, high density lipoprotein cholesterol (HDL-C) was higher (p less than 0.01) than in the normoxic condition, but there were no changes in serum lipids and glucose, or liver and aorta cholesterol. Skeletal muscle TG and liver glycogen in hyperoxic condition tended to show the higher values. Basal lipolysis of adipose tissue was increased (p less than 0.05) by hyperoxia, and decreased (p less than 0.01) by training, but there was no change of norepinephrine induced lipolysis in any group. The results suggest that endurance training or resting under hyperoxia induces increased HDL-C or lipolytic activity of adipose tissue. These effects might be caused by greater fat oxidation during exercising or resting under hyperoxia.

Adipose Tissue↗
PubMed1989

Effects of hyperoxia on the oxygen distribution in the intact cat retina.

Double-barreled oxygen microelectrodes were used to measure the distribution of oxygen within the dark adapted cat retina during systemic hyperoxia (100% O2 inspired). Oxygen tension (PO2) decreased monotonically from the choroid to the vitreous humor in most cases, showing that a greater portion of the retina was supplied by the choroid during hyperoxia than during normoxia. In the proximal half of the retina the PO2 increased during hyperoxia by an average of about 40 mm Hg, while the increase in the distal retina was larger. At the choroid the average increase in PO2 was about 150 mm Hg. Analysis of the oxygen profiles showed that photoreceptor oxygen consumption was unchanged during hyperoxia. Retinal PO2 increased rapidly at the beginning of hyperoxia, and often partially recovered from its peak value during hyperoxia, even in the distal retina, suggesting that the choroidal circulation may have some limited autoregulatory capacity. As in normoxia, retinal illumination led to an increase in PO2 in the distal retina, due to a decrease in oxygen consumption. The light-evoked increase in PO2 was larger during hyperoxia, but the underlying change in oxygen consumption was probably the same as in normoxia.

Animals↗
PubMed1985

Oxygen toxicity and restructuring of pulmonary arteries--a morphometric study. The response to 4 weeks' exposure to hyperoxia and return to breathing air.

This study describes the pulmonary vascular lesions in rat pulmonary arteries and altered right ventricular weight after 1) prolonged exposure to hyperoxia (87% O2 for 4 weeks) at ambient pressure, 2) weaning from hyperoxia to air over 7 days, and 3) return to breathing air for 2, 4, or 8 weeks. Hyperoxia for 28 days narrows the lumen of intraacinar and preacinar arteries, increasing the percent medial thickness (%MT) by reducing the external diameter and thickening medial muscle. The ratio of patent intraacinar arteries to alveoli is significantly reduced, and pulmonary vascular obstruction and obliteration is evident by electron microscopy. A higher proportion of intraacinar and preacinar arteries have muscle in their wall than in the normal lung: in alveolar wall and duct regions, the proportion of partially muscular and muscular intraacinar arteries increases at the expense of nonmuscular ones (for both regions P chi 2 less than or equal to 0.001); and in arteries associated with terminal bronchioli and bronchioli the proportion of muscular arteries increases at the expense of partially muscular ones (for both regions P chi 2 less than or equal to 0.001). Both after weaning and after return to breathing air lumen size increases; but, even after 8 weeks, the %MT remains significantly increased, and the ratio of intraacinar arteries to alveoli is less than normal. After weaning, the proportion of muscularized intraacinar and preacinar arteries is similar to that after hyperoxia. Two weeks after return to breathing air, the proportion of muscularized alveolar wall and duct arteries is greater (for both regions P chi 2 less than or equal to 0.001). Even 8 weeks after return to breathing air more arteries are muscularized than normal (for both alveolar wall and duct regions P chi 2 less than or equal to 0.001), and within the alveolar wall still more are muscularized than after hyperoxia (P chi 2 less than or equal to 0.001). Hyperoxia causes right ventricular hypertrophy, reducing the ratio of the weight of the left ventricle and septum to that of the right ventricle (P chi 2 less than or equal to 0.001). Weaning further increases the hypertrophy, the ratio being further reduced (P chi 2 less than or equal to 0.001, compared with both hyperoxia and control values). On return to breathing air the degree of hypertrophy is less, but it persists, and even after 8 weeks the ratio is still less than normal (P chi 2 less than or equal to 0.01).

Animals↗
PubMed2002

Pharmacologically induced relaxation of tracheal smooth muscle is increased in hyperoxia-exposed 15-day-old rats.

Hyperoxia increases maximum airway contractility in newborn guinea pigs and immature rats. Studies examining the mechanisms of hyperoxia-induced airway hyperresponsiveness have focused on contractile mechanisms, although excessive airway narrowing could be due to impaired relaxation. Our objective was to determine the effects of hyperoxia on airway structure and relaxing properties in juvenile rats exposed to an inspired fraction of oxygen (FiO(2)) of 0.5 within 24 hr of birth for 15 days, compared to a control group of air-exposed rats. We studied the 1) tracheal smooth muscle surface area; and 2) in vitro relaxation in precontracted (carbachol, 1.10(-3) M) isolated tracheal rings to increasing cumulative concentrations (10(-8) to 10(-4) M) of salbutamol. There was no significant difference in the amount of smooth muscle between the hyperoxia and air-exposed groups. Maximal relaxation of the isolated trachea to salbutamol was greater in the hyperoxia group than in the air-exposed group when normalized to smooth muscle surface area (-12.69 +/- 3.51 g/mm(2) vs. - 8.49 +/- 1.67 g/mm(2); P (MANOVA) < 0.05) or expressed as maximal relaxation induced by 10(-3) M theophylline (61% vs. 28%; P < 0.05). In conclusion, salbutamol-induced relaxation is enhanced (and not impaired) in newborn rats exposed to prolonged moderate hyperoxia.

Adrenergic beta-Agonists↗
PubMed2006

Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, prevents hyperoxia-induced neonatal rat lung injury in vivo.

Molecular disruption of homeostatic alveolar epithelial-mesenchymal interactions results in transdifferentiation of alveolar interstitial lipofibroblasts to myofibroblasts. Although this process was suggested to be a central molecular event in the pathogenesis of bronchopulmonary dysplasia (BPD), so far it has been only demonstrated in vitro; whether it also occurs in vivo is unknown. Our objectives were to determine if exposure to hyperoxia results in pulmonary alveolar lipo-to-myofibroblast transdifferentiation in vivo, and whether treatment with a potent peroxisome proliferator-activated receptor gamma (PPARgamma) (the key lipogenic fibroblast nuclear transcription factor) agonist, rosiglitazone, prevents this process. Newborn Sprague Dawley rat pups were exposed to control (21% O2), hyperoxia alone (95% O2 for 24 hr), or hyperoxia with rosiglitazone (95% O2 for 24 hr + rosiglitazone, 3 mg/kg, administered intraperitoneally) conditions. Subsequently, pups were sacrificed, and lung tissue was analyzed by morphometry, and by reverse transcription-polymerase chain reaction, Western hybridization, and immunohistochemistry for the expression of key lipogenic and myogenic markers. We observed a significant decrease in the expression of lipogenic markers, and a significant increase in the expression of myogenic markers in the hyperoxia-alone group. These hyperoxia-induced morphologic, molecular, and immunohistochemical changes were almost completely prevented by rosiglitazone. This is the first evidence of in vivo lipo-to-myofibroblast transdifferentiation and its almost complete prevention by rosiglitazone, prompting us to conclude that administration of PPARgamma agonists may be a novel, effective strategy to prevent the hyperoxia-induced lung molecular injury that has been implicated in the pathogenesis of BPD.

Actins↗
PubMed1996

Endotoxin treatment increases lung mitochondrial scavenging of extramitochondrial superoxide in hyperoxia-exposed rats.

Mitochondria scavenge extramitochondrial superoxide anion via a respiration-dependent (i.e., non-enzymatic) mechanism. This study reports that hyperoxia exposure ( > 95 % O2 for 48h) reduced (P < 0.05) lung mitochondrial respiration-dependent superoxide scavenging by 56% compared to lung mitochondria from untreated control rats. In comparison, endotoxin treatment (5 micrograms insufflated intratracheally 24 h earlier) increased (P < 0.05) lung mitochondrial respiration-dependent superoxide scavenging by 57% compared to mitochondria from untreated control rats. Further, lung mitochondria from rats given endotoxin 24 h prior to hyperoxia exposure had more than twice the respiration-dependent superoxide scavenging capacity as compared to mitochondria from untreated rats exposed to hyperoxia (P < 0.05). In contrast, endotoxin treatment did not increase (P < 0.05) lung mitochondrial enzymatic (i.e., superoxide dismutase) scavenging activity when corrected for mitochondrial protein content in either hyperoxia-exposed or air-exposed rats. Therefore, hyperoxia exposure decreased, whereas endotoxin treatment increased, respiration-dependent lung mitochondrial scavenging of extramitochondrial superoxide. This recently identified cellular antioxidant defense appears to be an early target in hyperoxia but its induction provides an important component of endotoxin-induced tolerance to hyperoxic lung damage.

Animals↗
PubMed1998

Identification of urokinase as a hyperoxia-inducible gene.

Hyperoxia has deleterious effects on lung form and function; however, the molecular events initiated by oxygen exposure remain unclear. We hypothesized that macrophages function as important intermediaries in the protective response of lung tissues after exposure to hyperoxia. This hypothesis was tested by exposing cultured macrophages (RAW 264.7 cells) to hyperoxia for 24 h and then applying the conditioned medium from these cells to cultured pulmonary epithelial cells or to pulmonary microvascular endothelial cells. We observed that the expression of manganese superoxide dismutase mRNA increased in both target cell lines. Therefore, we next hypothesized that exposure of these macrophages to hyperoxia results in a change in gene expression which could be detected by differential display PCR (ddPCR). This hypothesis was tested by exposing RAW 264.7 cells to > or = 95% oxygen (or normoxia) for 24 h, harvesting RNA, and performing ddPCR. A cDNA fragment upregulated by hyperoxia was identified and reamplified. Verification of differential expression of mRNA was done by Northern analysis. A mRNA which was reproducibly upregulated by hyperoxia, as well as by lipopolysaccharide and interferon gamma, was identified. The differentially expressed PCR product was cloned and sequenced, revealing a product with 99% identity to mouse urokinase mRNA. We speculate that one function of pulmonary macrophages following a hyperoxic exposure is to secrete urokinase.

Animals↗
PubMed2002

Effects of moderate hyperoxia on oxygen consumption during submaximal and maximal exercise.

The present study examined the effect of hyperoxia on oxygen uptake (VO(2)) and on maximal oxygen uptake (VO(2max)) during incremental exercise (IE) and constant work rate exercise (CWRE). Ten subjects performed IE on a bicycle ergometer under normoxic and hyperoxic conditions (30% oxygen). They also performed four 12-min bouts of CWRE at 40, 55, 70 and 85% of normoxic VO(2max) (ex1, ex2, ex3 and ex4, respectively) in normoxia and in hyperoxia. VO(2max) was significantly improved by 15.0 (15.2)% under hyperoxia, while performance (maximum workload, W(max)) was improved by only +4.5 (3.0)%. During IE, the slope of the linear regression relating VO(2) to work rate was significantly steeper in hyperoxia than in normoxia [10.80 (0.88) vs 10.06 (0.66) ml x min(-1) x W(-1)]. During CWRE, we found a higher VO(2) at ex1, ex2, ex3 and ex4, and a higher VO(2) slow component at ex4 under hyperoxia. We have shown that breathing hyperoxic gas increases VO(2max), but to an extent that is difficult to explain by an increase in oxygen supply alone. Changes in metabolic response, fibre type recruitment and VO(2) of non-exercising tissue could explain the additional VO(2) for a given submaximal work rate under hyperoxia.

Adult↗
PubMed2005

Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia.

S-Adenosylmethionine (SAM, AdoMet) is the most important methyl donor used for synthesis of nucleic acids, phospholipids, creatine, and polyamines and for methylation of many bioactive molecules. The metabolic response of the lung to oxidative stress of hyperoxia requires increased RNA and protein synthesis for energy metabolism, growth arrest, and antioxidant defense. We studied the production of SAM and other aspects of methionine metabolism in lung epithelial cells exposed to hyperoxia. Human lung epithelial-like (A549) and primary small airway epithelial (SAE) cells were exposed to normoxia (21% O(2)) or hyperoxia (95% O(2)). Cell methionine and S-adenosylmethionine content increased in response to hyperoxia in SAE and A549 cells. Because methionine adenosyl transferase (MAT) is the rate-limiting enzyme of the pathway, we examined the expression of a lung epithelial isoform of MAT 2A in hyperoxia. Western blots revealed a novel MAT 2A isoform expressed in both cell types, with a lower molecular mass than that described in Jurkat cells. Cloning and sequencing of the MAT 2A cDNA revealed one silent nucleotide substitution compared to that expressed in Jurkat. The lower mass of MAT 2A in both lung epithelial cells indicated that the absence of the major posttranslational modification of MAT 2A found in Jurkat. MAT 2A protein progressively increased during hyperoxic exposure in both transformed and primary lung epithelium. Increased flux of (13)C-labeled methionine to S-adenosylhomocysteine (SAH) in A549 demonstrated that SAM's methyl group was utilized, and increased formation of cystathionine indicated that at least part of SAM generated was directed toward cysteine/GSH in the transsulfuration pathway. These results indicate activation of MAT 2A and the transmethylation pathway in the metabolic response to hyperoxia in lung epithelium.

Cell Line, Tumor↗