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Carroll E Cross

Publications and source records attributed to Carroll E Cross.

34 records · Page 2Linked to original sources
PubMed2003

5-nitro-gamma-tocopherol increases in human plasma exposed to cigarette smoke in vitro and in vivo.

We hypothesized that the high concentrations of reactive nitrogen species in cigarette smoke and the known stimulatory effects of cigarette smoke on the inflammatory immune systems would lead to the formation of 5-nitro-gamma-tocopherol (NGT). In order to assess gamma-tocopherol nitration, human plasma was exposed in vitro to gas phase cigarette smoke (GPCS) or air for up to 6 h. A liquid chromatography-mass spectrometry (LC-MS) method was developed to quantitate NGT. Detector response was linear from 0.1 to 3 pmol NGT, with a detection limit of 20 fmol. After a 1 h lag time, 6 h plasma exposure to GPCS depleted approximately 75% of alpha-T, approximately 60% of gamma-T and increased NGT from 3 to 134 nmol/l. The increase in NGT accounted for approximately 20% of the gamma-T decrease. NGT also correlated (R2 = 0.9043) with nitrate concentrations in GPCS-exposed plasma. The physiologic relevance of NGT was evaluated in a group of healthy humans. Smokers (n = 15) had plasma NGT concentrations double those of nonsmokers (n = 19), regardless of corrections using lipids or gamma-T; plasma alpha-T and gamma-T concentrations were similar between the groups. Our results show that LC-MS can be successfully used for NGT quantitation in biologic samples. Importantly, NGT in smokers' plasma suggests that cigarette smoking causes increased nitrosative stress.

Humans↗
PubMed2003

Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in alpha-tocopherol transfer protein.

Alpha-tocopherol transfer protein (TTP) regulates the retention and secretion of alpha-tocopherol (alpha-T) by the liver. Deletion of the TTP gene (Ttpa) in mice results in systemic deficiency of alpha-T and neurological dysfunctions described in patients with mutated Ttpa. We have explored genome-wide changes in mRNAs from brain cortex and liver of Ttpa-deficient (Ttpa(-/-)) mice and wild-type (Ttpa(+/+)) mice. Selective inductions of genes regulated by antioxidant response elements were detected in Ttpa(-/-) livers compared to Ttpa(+/+) livers, suggesting increased oxidant stress in Ttpa(-/-) livers. The activation of cell proliferation pathways in Ttpa(-/-) livers was indicated by the induction of genes that encode growth factor-binding proteins, mitogen-activated protein kinase kinase 3, and apoptosis inhibitor 6. The induction of synuclein-alpha and repression of synuclein-beta genes was detected in Ttpa(-/-) cortex. This may predispose Ttpa(-/-) cortex to increased formation of synuclein-alpha aggregates and Lewy body, often associated with oxidant stress. Cortex of Ttpa(-/-) mice revealed repression of genes encoding synaptic proteins, protein kinase C family members, and myelin proteins. A 13-fold decrease in the expression of retinoic acid receptor-related orphan receptor-alpha mRNA predicts staggerer-like phenotype (ataxia and deficits of motor coordination) of Ttpa(-/-) mice. The repression of specific genes that determine synaptic plasticity and neuronal development may account for suppressed electrophysiological activities of cortex and impaired behavior in Ttpa(-/-) mice.

Animals↗
PubMed2003

Induction of stress proteins and MMP-9 by 0.8 ppm of ozone in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant pollutants to which cutaneous tissues are exposed. O(3) exposure has been shown to induce antioxidant depletion as well as the oxidation of lipids and proteins within the outermost skin layer, the stratum corneum. However, relatively little is known regarding the potential effects of O(3) on the cellular constituents of the underlying skin epidermis and dermis. In the present study, hairless mice exposed for 6 h to 0.8 ppm O(3) showed increases in lipid peroxidation, as quantitated by increases in 4-hydroxynonenal-protein adducts. O(3) exposure caused an induction of the stress proteins HSP27 and heme oxygenase-1 (HO-1), starting at 6 h and increasing up to 18 h after O(3) exposure. This was accompanied by an increase in matrix metalloproteinase-9 (MMP-9) mRNA and activity levels, indicative of possible injurious-reparative processes. Collectively, our data demonstrate that skin exposure to O(3) not only affects antioxidant levels and oxidation markers in the outermost stratum corneum layer, but also induces cellular stress responses in the deeper cellular layers of the skin.

Animals↗
PubMed2003

Ozone-induced disruptions of lung transcriptomes.

We have analyzed changes in approximately 4000 lung mRNAs, with GeneChips, in mice exposed to 1 ppm O(3) for three consecutive nights (8 h per night). Differential gene expression analysis identified approximately 260 O(3) sensitive genes; approximately 80% of these were repressed and approximately 20% were induced in O(3)-exposed mice compared to the air-exposed controls. A 20-fold induction of serum amyloid A3 mRNA by O(3) suggested activation of NF-kappaB and CCAAT/enhancer binding protein-mediated pathways by inflammatory cytokines. Induction (up to 14-fold) of 12 genes that increase DNA synthesis and cell cycle progression, and increase (approximately 7-fold) in CD44 mRNA and macrophage metalloelastase suggested a state of O(3)-induced hyperplasia and lung remodeling. Several mRNAs encoding enzymes of xenobiotic metabolism and cytoskeletal functions were repressed and may suggest cytokine mediated suppression of cytochrome P450 expression and cachexia-like inflammatory state in ozone-exposed lungs. The expressions of approximately 30 genes of immune response were also repressed. Collectively this genome-wide analysis of lungs identified ozone-induced disruption of gene transcriptional profile indicative of increased cellular proliferation under suppressed immune surveillance and xenobiotic metabolism.

Air↗
PubMed2003

Cytokine induction of prolactin receptors mediates prolactin inhibition of nitric oxide synthesis in pulmonary fibroblasts.

Prolactin (PRL) has been implicated as a modulator of immune function, and some of its actions may be linked to NO synthesis. Because NO acts as a mediator of inflammation, we speculated that an inflammatory milieu could unmask pathways by which PRL could affect NO synthesis. Here, we show that pro-inflammatory cytokines induce the expression of PRL receptors in pulmonary fibroblasts, allowing PRL to inhibit cytokine-induced NO production and the expression of the inducible nitric oxide synthase (iNOS). Inhibition of iNOS expression by PRL correlates with the phosphorylation of STAT-5b (signal transducer and activator of transcription 5b) and the suppression of expression of IRF-1 (interferon regulatory factor 1), a transcription factor for iNOS. These results reveal previously unrecognized mechanisms by which PRL and PRL receptors may play significant modulatory roles during immune-inflammatory processes.

Animals↗
PubMed2003

Inhibition of oral peroxidase activity by cigarette smoke: in vivo and in vitro studies.

Oral peroxidase (OPO), the pivotal enzyme in the salivary antioxidant system, seems to be of paramount importance in the oral defense mechanism, especially against the attack of free radicals related to cigarette smoke (CS) and the evolution of oral cancer. The major inducer of oral cancer is exposure to tobacco, which is responsible for 50-90% of cases worldwide. The purpose of our study was to elucidate the outcome of interaction between CS and OPO in smokers and nonsmokers. After smoking a single cigarette, a sharp drop of OPO activity was observed in both groups: 42.5% in smokers and 58.5% in nonsmokers (p <.05). After 30 min, the level of activity returned to 90-100% of the presmoking level, presumably due to the secretion of new saliva into the oral cavity. The difference between the two groups was also observed after exposure of saliva to one cigarette in smoking flasks (in vitro studies); however, as expected, no recovery of activity was observed in either group. Similarly, the OPO activity loss was accompanied by increased carbonylation of the salivary proteins, an indicator of the oxidative damage to proteins. These results may be of great clinical importance, as heavy smokers smoke 20 cigarettes or more on a daily basis. Accordingly, most of the time the oral epithelium of heavy smokers is essentially unprotected by OPO against the deleterious effects of thiocyanate ions and hydroxyl radicals produced by unremoved hydrogen peroxide in the presence of the salivary redox-active metal ions. This may pave the way for the CS-induced and saliva-mediated initiation and progression of oral cancer.

Antioxidants↗
PubMed2003

Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes.

BACKGROUND: Free radicals in cigarette smoke may cause oxidative damage to macromolecules, contributing to cardiovascular diseases and cancer. Decreased plasma antioxidant concentrations may indicate cigarette smoke-related oxidative stress. OBJECTIVE: We compared the effects on plasma antioxidant concentrations in cotinine-confirmed active and passive smokers with those in nonsmokers, independent of differences in dietary intakes and other covariates. DESIGN: Plasma samples from 83 smokers, 40 passive smokers, and 36 nonsmokers were analyzed for total ascorbic acid, alpha- and gamma-tocopherols, 5 carotenoids, retinol, and cotinine. Groups were compared by using analysis of variance with adjustment for sex, age, race, body mass index, alcohol intake, triacylglycerol concentration, fruit and vegetable intakes, and dietary antioxidants. RESULTS: After adjustment for dietary antioxidant intakes and other covariates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro mol/L, respectively). Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than did nonsmokers and passive smokers (ascorbic acid: 43.6, 54.5, and 54.6 micro mol/L, respectively; beta-cryptoxanthin: 0.12, 0.16, and 0.16 micro mol/L, respectively) and significantly lower concentrations of lutein and zeaxanthin than did nonsmokers (0.33 compared with 0.41 micro mol/L). The P values for all the differences described above were < 0.05. No significant differences in plasma concentrations of alpha-tocopherol, alpha-carotene, total carotenoids, lycopene, or retinol were observed. CONCLUSIONS: These results indicate that cigarette smokers and nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than do unexposed nonsmokers, independent of differences in dietary antioxidant intakes. Further research is required to explain why plasma gamma-tocopherol concentrations were significantly higher in smokers and passive smokers than in nonsmokers.

Adult↗
PubMed2003

Lycopene inhibits the growth of normal human prostate epithelial cells in vitro.

Lycopene has repeatedly been shown to inhibit the growth of human prostate cells in vitro. However, previous studies with lycopene have focused on cancer specimens, and it is still unclear whether this carotenoid affects the growth of normal human prostate cells as well. Therefore, we investigated the effects of lycopene on normal human prostate epithelial cells (PrEC) by treating them with synthetic all-E-lycopene (up to 5 micromol/L) and assessing proliferation via [3H]thymidine incorporation. The effects of lycopene on cell cycle progression were investigated via flow cytometry. To elucidate whether lycopene modulates cyclins involved in cell cycle progression, protein expressions of cyclins D1 and E were analyzed. The results show that lycopene significantly inhibited the growth of PrEC in a dose-dependent fashion. Flow cytometry revealed a significant cell cycle arrest in the G0/G1 phase. This effect was confirmed by inhibition of cyclin D1 protein expression, whereas cyclin E levels remained unchanged. The results demonstrate that lycopene inhibits growth of nonneoplastic PrEC in vitro. We hypothesize that lycopene might likewise inhibit the growth of prostatic epithelial cells in vivo. This might have an effect on prostate development and/or on enlargement of prostate tissue as found in benign prostate hyperplasia, a potential precursor of prostate cancer.

Antioxidants↗
PubMed2003

Cystic fibrosis in adults: current and future management strategies.

Over 30,000 individuals in the United States of America are living with cystic fibrosis (CF). Despite incremental advances in care and understanding of its pathophysiology, CF remains a significantly life-limiting disease. Readily accessible newborn screening, genetic testing, and an improved awareness have increased the early recognition of CF, atypical presentations of CF, and the CF-related diseases. Improvements in medical management have led to continually improving life expectancy for patients with CF. Despite improved management strategies, severe lung disease remains the commonly life-limiting pathology. We review the pathophysiology, diagnosis, and management of the respiratory-tract manifestations of CF that represent the life-limiting aspects of the condition and summarize upcoming and possible future therapies for patients with CF.

Adult↗
PubMed2002

Environmental oxidant pollutant effects on biologic systems: a focus on micronutrient antioxidant-oxidant interactions.

Oxidative atmospheric pollutants represent a significant source of stress to both terrestrial plants and animals. The biosurfaces of plants and surface-living organisms are directly exposed to these pollutant stresses. These surfaces, including respiratory tract surfaces, contain integrated antioxidant systems that would be expected to provide a primary defense against environmental threats caused by atmospheric reactive oxygen species. When the biosurface antioxidant defenses are overwhelmed, oxidative stress to the cellular components of the exposed biosurfaces can be expected, inducing inflammatory, adaptive, injurious, and reparative processes. Studies of mutants and/or transformed plants and insects, with specific alterations in key components of antioxidant defense systems, offer opportunities to dissect the complex systems that maintain surface defenses against environmental oxidants. In this article, we use a comparative approach to consider interactions of atmospheric oxidant pollutants with selected biosystems, with focus on O3 as the pollutant; plants, flies, skin, and lungs as the exposed biosystems; and nonenzymatic micronutrient antioxidants as significant contributors to overall antioxidant defense strategies of these varied biosystems. Parallelisms among several living organisms, with regard to their protective strategies against environmental atmospheric oxidants, are presented.

Animals↗
PubMed2002

Identification of glutathione modifications by cigarette smoke.

Although it has been recognized for decades that cigarette smoke (CS) is toxic to respiratory tract tissues, and that glutathione (GSH) and other thiols are able to ameliorate some of the adverse effects of CS, the precise interactions between thiols and critical CS components are only partially characterized. In the present study, we used HPLC and MALDI-MS approaches to more rigorously characterize the products of CS reactions with GSH, the major cellular thiol and an important antioxidant constituent in respiratory tract lining fluids, in an attempt to increase our understanding of mechanisms of CS respiratory tract toxicity. Exposure of solutions of GSH to gas phase CS resulted in its rapid depletion, and about 50% of this depletion could be accounted for by reaction with acrolein and crotonaldehyde, the two major alpha, beta-unsaturated aldehydes in CS. Similar aldehyde adducts with GSH could also be detected in cells exposed to CS, although the relative yields were limited, presumably because of further reactions of these adducts and/or their excretion. Further characterization of in vivo thiol-aldehyde formation in respiratory tract cells can be expected to provide significant insights into the mechanisms of CS toxicity.

Aldehydes↗
PubMed2002

Ozone exposure activates oxidative stress responses in murine skin.

Ozone (O(3)) is among the most reactive environmental oxidant to which skin is exposed. O(3) exposure has previously been shown to induce antioxidant depletion as well as lipid and protein oxidation in the outermost skin layer, the stratum corneum (SC), but little is known regarding the potential effects of O(3) on the skin epidermis and dermis. To evaluate such skin responses to O(3), SKH-1 hairless mice were exposed for 2 h to 8.0 ppm O(3) or to ambient air. O(3) exposure caused a significant increase in skin carbonyls (28%) compared to the skin of air exposed control animals. An evident increase in 4-hydroxynonenal-protein adducts was detected after O(3) exposure. O(3) exposure caused a rapid up-regulation of HSP27 (20-fold), and more delayed induction of HSP70 (2.8-fold) and heme oxygenase-1 (5-fold). O(3) exposure also led to the induction of nitric oxide synthase (iNOS) 6-12 h following O(3) exposure. We conclude that skin exposure to high levels of O(3) not only affects antioxidant levels and oxidation markers in the SC, but also induces stress responses in the active layers of the skin, most likely by indirect mechanisms, since it is unlikely that O(3) itself penetrates the protective SC layers.

Aldehydes↗
PubMed2002

Lung tumor development in mice exposed to tobacco smoke and fed beta-carotene diets.

In human clinical trials it was found that the putative chemopreventive agent beta-carotene not only failed to protect active smokers against the carcinogenic action of tobacco smoke, but actually increased their risk of developing lung cancer. In preclinical animal studies, beta-carotene had been effective against some chemically induced cancers, but not against tumors in the respiratory tract. We exposed male strain A/J mice to tobacco smoke at a concentration of 140 mg/m(3) of total suspended particulate matter, 6 h a day, 5 days a week, for either 4 or 5 months, followed by a recovery period in air for 4 or 5 months, or for 9 months without recovery period. beta-carotene was added in the form of gelatin beadlets to the AIN-93G diet either during or following tobacco smoke exposure at concentrations of 0.005, 0.05 and 0.5%. In the supplement-fed animals, plasma and lung levels of beta-carotene were higher than they were in animals fed control diets. Exposure to tobacco smoke increased rather than decreased plasma beta-carotene levels, but had no significant effect on lung levels. After 9 months, lung tumor multiplicities and incidence were determined. Tobacco smoke increased both lung tumor multiplicities and incidences, but beta-carotene failed to modulate tumor development under all exposure conditions. Animal studies in a model of tobacco smoke carcinogenesis would thus have predicted the absence of any beneficial effects of beta-carotene supplementation in current or former smokers, but would have failed to anticipate the increase in lung cancer risk.

Animals↗
PubMed2002

Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers.

Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, alpha-lipoic acid, and vitamin E decreases plasma F(2)-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20-78 years) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F(2)-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases.

Adult↗
PubMedDate not supplied

Inhibition of NFkappaB activation and IL-8 expression in human bronchial epithelial cells by acrolein.

Lipid oxidation and environmental pollutants are major sources of alpha,beta-unsaturated aldehydes such as acrolein and 4-hydroxynonenal. Acrolein (2-propenal), a major product of organic combustion such as tobacco smoke, represents the most reactive alpha,beta-unsaturated aldehyde, with high reactivity toward nucleophilic targets such as sulfhydryl groups. To investigate how acrolein affects respiratory tract cell activation, we exposed either primary (NHBE) or immortalized human bronchial epithelial cells (HBE1) to 0-25 microM acrolein, and determined effects on basal and tumor necrosis factor-alpha (TNFalpha)-induced production of the chemokine interleukin (IL)-8. Cell exposure to acrolein dose-dependently suppressed IL-8 mRNA levels in HBE1 cells (26, 40, and 79% at 5, 10, and 25 microM acrolein concentrations, respectively) and resulted in corresponding decreases in IL-8 production. Studies of nuclear factor-kappaB (NFkappaB) activation, an essential event in IL-8 production, showed decreased TNFalpha-induced NFkappaB activation by acrolein, illustrated by inhibition of nuclear translocation of NFkappaB and reduced IkappaBalpha degradation. Immunochemical analysis of IkappaB kinase (IKK), a redox-sensitive regulator of NFkappaB activation, indicated direct modification of the IKK beta-subunit by acrolein, suggesting that acrolein may act directly on IKK. In summary, our results demonstrate that acrolein can suppress inflammatory processes in the airways by inhibiting epithelial IL-8 production through direct or indirect inhibitory effects on NFkappaB activation.

Acrolein↗