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1.
J Appl Physiol (1985) ; 107(1): 54-62, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19074571

RESUMO

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.


Assuntos
Repouso em Cama/efeitos adversos , Gravidade Alterada , Estado Nutricional/fisiologia , Contramedidas de Ausência de Peso , Adulto , Antioxidantes/análise , Análise Química do Sangue , Ingestão de Alimentos , Ingestão de Energia/fisiologia , Testes Hematológicos , Humanos , Masculino , Oligoelementos/sangue , Vitaminas/sangue , Ausência de Peso/efeitos adversos , Simulação de Ausência de Peso
2.
J Parasitol ; 101(4): 405-17, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25932498

RESUMO

Organisms face a multitude of potential stressors, and the way these stressors interact can provide insights into underlying biological processes. This study examined the flour beetle Tribolium confusum and its survival, net fecundity, and surface-seeking behavior in response to combinations of stressors from 3 categories. Infection by the cestode Hymenolepis diminuta provided a stress of parasitic origin. Exposure to diatomaceous earth (DE) provided a stress of environmental origin. Use of virgin and mated beetles evaluated reproduction as a stress of host origin. Single and multiple exposure of beetles to parasite eggs achieved a maximum mean abundance of 21 parasites/beetle and a maximum intensity of 90 parasites in an individual beetle. DE reduced initial parasite establishment, but did not directly affect survival of parasites after their establishment in the host. A rehydration technique was used to recover parasites from dead beetles, enabling this to be the first study to correlate H. diminuta intensity at time of death directly to mortality of T. confusum. A dichotomous intensity-mortality relationship was observed in 8% DE, whereby lightly infected (<20 parasites) hosts were killed by DE in an intensity-independent manner, but more heavily infected hosts were killed in an intensity-dependent manner. Host mating status did not affect host survival, but there were interactions among mating status, parasitism, and DE on net fecundity and surface-seeking behavior. However, these effects were minor compared to the host mortality that occurred when parasite abundance and DE concentration were both high. The aggregated distribution of T. confusum in beetles, the difficulty of achieving high mean abundances, and an apparent need for the stressors to have strong effects individually if they are to have enhanced effects when in combination, suggests that exposure to multiple stressors would seriously impact only a small proportion of the host population.


Assuntos
Terra de Diatomáceas/metabolismo , Hymenolepis diminuta/fisiologia , Tribolium/fisiologia , Tribolium/parasitologia , Análise de Variância , Animais , Meio Ambiente , Feminino , Interações Hospedeiro-Parasita , Masculino , Distribuição Aleatória , Reprodução/fisiologia , Fatores Sexuais , Fatores de Tempo
3.
Endocrinology ; 141(11): 4270-7, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11089562

RESUMO

Mice deficient in gamma-glutamyl transpeptidase (GGT) are growth retarded as a result of cysteine deficiency secondary to excessive glutathione excretion in urine and display coat color defects and cataracts. Although GGT is widely expressed throughout the mouse reproductive axis, little is known about its role in reproduction. Here, we present an analysis of the reproductive phenotypes of GGT-deficient mice. Mutant male mice have reduced testis and seminal vesicle size and suppressed serum insulin-like growth factor I and FSH levels and are infertile. Although these mice are severely oligospermic, histological analysis of testes reveals grossly normal stages of spermatogenesis, including late stage spermatids, but the tubule diameter is reduced. GGT-deficient female mice are also hypogonadal and infertile. At 6 weeks of age, the ovaries of mutant mice are histologically indistinguishable from those of its wild-type counterpart. However, the absence of antral follicles and corpora lutea and follicular degeneration are apparent by 11-13 weeks. In addition, immature female mutant mice (at 21-23 days) are insensitive to exogenous gonadotropin administration and fail to superovulate, suggesting an intraovarian defect. Consistent with these mutant phenotypes, HPLC analysis of adult mutant testes and ovaries showed a reduction in intracellular cysteine levels. Administration of N-acetylcysteine in the drinking water beginning on day 21 to mutant mice for 2 weeks restored testis, seminal vesicle, and ovary sizes to values comparable to those in wild-type mice. Furthermore, N-acetylcysteine-fed (continuously) mutant male and female mice were fertile and produced normal numbers of offspring when mated to wild-type control mice. These results demonstrate that GGT itself is not necessary for reproductive function. However, GGT plays an important role in cysteine homeostasis within the mouse reproductive axis.


Assuntos
Infertilidade Feminina/etiologia , Infertilidade Masculina/etiologia , Reprodução , gama-Glutamiltransferase/deficiência , Acetilcisteína/farmacologia , Animais , Cisteína/análise , Feminino , Hormônio Foliculoestimulante/sangue , Transtornos do Crescimento/etiologia , Hormônio do Crescimento/sangue , Infertilidade Feminina/patologia , Infertilidade Feminina/fisiopatologia , Infertilidade Masculina/patologia , Fator de Crescimento Insulin-Like I/análise , Masculino , Camundongos , Camundongos Knockout , Oligospermia/etiologia , Folículo Ovariano/fisiopatologia , Ovário/química , Ovário/patologia , Glândulas Seminais/química , Testículo/química , Testículo/patologia , gama-Glutamiltransferase/genética , gama-Glutamiltransferase/fisiologia
4.
Environ Health Perspect ; 107(2): 161-5, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9924013

RESUMO

To examine the toxicity of cyclosiloxanes (CSs), the predominant low molecular weight cyclic silicones found in breast implants, we injected female CD-1 mice intraperitoneally with different doses of distillate (3.5-35 g/kg body weight) containing cyclosiloxane D3 (hexamethylcyclotrisiloxane; CS-D3), cyclosiloxane D4 (octamethylcyclotetrasiloxane; CS-D4), cyclosiloxane D5 (decamethylcyclopentasiloxane; CS-D5), and cyclosiloxane D6 (dodecamethylcyclohexasiloxane; CS-D6). The distillate was found to be lethal and all the mice injected with 35 g/kg died within 5-8 days. The median lethal dose (LD50) for distillate was estimated to be approximately 28 g/kg. These mice developed inflammatory lesions of the lung and liver as well as liver cell necrosis with elevated serum levels of alanine aminotransferase, aspartate aminotransferase, and lactic acid dehydrogenase. Administration of CS-D4 alone also produced lethality in these mice with an LD50 of 6-7 g/kg. CS-D4-treated mice also exhibited pulmonary and hepatic lesions and elevated serum enzymes. Analysis of LD50 data indicates that CS-D4 is about as toxic as carbon tetrachloride or trichloroethylene. We measured hydroxyl radical formation in CS-D4-treated mice and found increases of approximately 20-fold in liver and approximately 7-fold in lung on day 4 following injection. Our findings are significant because in vitro experiments have demonstrated that CSs can migrate out of breast implants, and in mouse experiments CSs have been shown to be widely distributed in many organs after a single subcutaneous injection and to persist for at least a year.


Assuntos
Materiais Biocompatíveis/toxicidade , Implantes de Mama/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Pneumopatias/induzido quimicamente , Siloxanas/toxicidade , Animais , Feminino , Radical Hidroxila/metabolismo , Dose Letal Mediana , Testes de Função Hepática , Pneumopatias/patologia , Camundongos
5.
Neurochem Int ; 36(3): 203-11, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10676854

RESUMO

Active potassium (K+) uptake and Na+,K+-ATPase activity were measured in primary cultures of mouse astrocytes. Both parameters were virtually unaffected by acute ammonia treatment but increased after chronic exposure to pathophysiologically relevant concentrations of ammonia (0.3 or 3 mM) for 1-4 days. The increased Na+,K+-ATPase activity after chronic treatment with ammonia was further enhanced in the acute presence of 12 mM K+. Based on these observations and literature data it was hypothesized that the direct effect of ammonia is formation of easily diffusible compound(s) with ouabain-like effect, that upregulation occurs of Na+,K+-ATPase activity and K+ uptake in response to the resulting ATPase inhibition, and that the washing procedure preceding the uptake experiments and the determination of Na+,K+-ATPase activity unmasks the upregulation. To test this hypothesis, the content of compounds with ouabain-like action was measured in media in which astrocytes had been incubated in the presence of 3 mM ammonia for 4 days and in controls to which an additional 3 mM NaCl had been added instead of ammonia. An endogenous, compound with ouabain-like activity was demonstrated both under control conditions and in the ammonia-treated cultures, and the content of this compound was increased by 50% in the ammonia-treated cultures. Preliminary experiments showed that at least part of the released ouabain-like compounds cross-react with authentic ouabain.


Assuntos
Amônia/farmacologia , Astrócitos/metabolismo , Ouabaína/metabolismo , Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Amônia/administração & dosagem , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Camundongos , Cloreto de Sódio/farmacologia
6.
Neurochem Int ; 37(2-3): 83-102, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10812194

RESUMO

A novel concept is described, according to which both neurons and astrocytes are capable of metabolizing glucose all the way to CO(2) and water, but in addition interact metabolically in a process generating glutamate from glucose, and subsequently, metabolizing excess glutamate to CO(2) and water Hertz, L., Dringen, R., Schousboe, A., Robinson, S.R., 1999. Astrocytes: Glutamate producers for neurons (Journal of Neuroscience Research 57, 417-428). The proposed metabolic degradation of glucose via glutamate serves the purpose of adjusting transmitter pools of glutamate to the demands for glutamatergic transmission, and it must account for a major fraction of glucose utilization. Evidence in favor of this concept is presented and a multitude of in vivo data are interpreted in the context of metabolic trafficking between neurons and astrocytes. In addition, intracellular trafficking occurs between cytosol and mitochondria during synthesis of transmitter glutamate, partly explaining a robust quantitative correlation between glutamine synthesis, as a measure of release of transmitter glutamate, and glucose utilization, reported by several authors. Both intracellular and intercellular metabolic trafficking may be affected during pathological conditions, as evidenced by effects of hyperammonemia (mimicking hepatic encephalopathy) and energy deprivation (mimicking stroke). It is suggested that neuronal-astrocytic interactions may also be impaired during degenerative dementing diseases.


Assuntos
Amônia/sangue , Astrócitos/fisiologia , Encéfalo/fisiologia , Citosol/metabolismo , Metabolismo Energético/fisiologia , Neurônios/fisiologia , Animais , Astrócitos/metabolismo , Glucose/deficiência , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Neurônios/metabolismo
7.
Brain Res Dev Brain Res ; 82(1-2): 62-8, 1994 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-7842520

RESUMO

The effect of 'simulated ischemia', i.e., combined anoxia and substrate deprivation, was studied in 1- and 3-week-old (i.e., immature and mature) primary cultures of mouse astrocytes. Cell survival, as indicated by retention of the high-molecular cytosolic protein lactate dehydrogenase was compared with retained high-energy phosphate compounds (ATP and phosphocreatine). A previously established longer survival of the immature cells during the metabolic insult was confirmed and found to correlate with a more complete maintenance of high-energy phosphates. However, in both the mature and immature cells, no death occurred as long as the ATP content remained at or above 25% of its control value. ATP concentrations below 10% of control were accompanied by almost complete cell death in both age groups. Thus, the better survival of immature astrocytes during simulated ischemia is correlated with better maintenance of the levels of high-energy phosphates and, regardless of age, cell death occurs only once a critically 'low' threshold of ATP has been reached.


Assuntos
Trifosfato de Adenosina/metabolismo , Astrócitos/metabolismo , Senescência Celular , Fosfocreatina/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Hipóxia Celular , Células Cultivadas , Metabolismo Energético , Isquemia , Cinética , L-Lactato Desidrogenase , Camundongos , Fatores de Tempo
8.
Mutat Res ; 447(2): 305-16, 2000 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-10751614

RESUMO

We have used a differential alkaline single cell gel electrophoresis assay of DNA ("omet assay" at pH 13 and 12.3) to evaluate DNA damage as a function of age in mice with an inherited defect in gluthathione (GSH) metabolism. The mice are homozygous null for gamma-glutamyltranspeptidase (GGT), the enzyme responsible for initiating the catabolism of GSH, and paradoxically have reduced levels of GSH and cysteine in many organs. We found an accumulation of DNA damage in lung, liver and kidney in these mice as a function of age. The largest differences were in assays run at pH 13, suggesting that the accumulation of apurinic/apryrimidinic (AP) sites and oxidative damage of DNA was largely responsible. In contrast, little if any accumulation of these lesions was detected in wild-type mice. Although these findings do not allow a precise analysis of the molecular basis of damage accumulation in GGT-deficient mice, they implicate low GSH and cysteine levels as a cause of accumulative DNA damage in the intact mammal.


Assuntos
Dano ao DNA , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , gama-Glutamiltransferase/deficiência , Envelhecimento , Álcalis/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Cisteína/metabolismo , DNA/efeitos dos fármacos , DNA/genética , Glutationa/metabolismo , Homozigoto , Rim/citologia , Rim/crescimento & desenvolvimento , Fígado/citologia , Fígado/crescimento & desenvolvimento , Pulmão/citologia , Pulmão/crescimento & desenvolvimento , Camundongos , Mutação , gama-Glutamiltransferase/genética
11.
Neurochem Res ; 19(3): 257-65, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7909919

RESUMO

Accumulation of radioactivity was studied in primary cultures of mouse astrocytes as a function of time of exposure (4-60 min) to 50 microM glutamate and 200 microM glutamine (initial concentrations), of which either glutamate or glutamine was 14C-labeled. Both the glutamate pool and the glutamine pool were compartmentalized. Initially, by far the major intracellular glutamate pool (> or = 90%) was derived from extracellular glutamate and could be converted to glutamine. This allowed a rather accurate determination of metabolic flux from glutamate to glutamine, which under control conditions amounted to 2.0-2.2 nmol/min per mg protein. After chronic exposure to 3 mM ammonia for 3 days this flux was significantly increased to 3.1-3.6 nmol/min per mg protein. Acute exposure to ammonia caused a smaller, apparent increase, which was not statistically significant. The glutamine content was compartmentalized at all stages of the incubation. It consisted of at least two different pools. One of these was accessible to extracellular glutamine and could be converted to intracellular glutamate (constituting a sizeable fraction of the total glutamate pool after longer incubation), whereas the other constituted endogenously derived glutamine, formed from accumulated glutamate. The specific activity of the precursor pool for glutamate synthesis could not be accurately determined and relatively exact fluxes therefore not be calculated. There was, however, no evidence that chronic exposure to ammonia decreases the rate of glutamine hydrolysis.


Assuntos
Amônia/toxicidade , Astrócitos/metabolismo , Encéfalo/metabolismo , Glutamatos/metabolismo , Glutamina/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Radioisótopos de Carbono , Células Cultivadas , Ácido Glutâmico , Cinética , Camundongos , Técnica de Diluição de Radioisótopos , Análise de Regressão , Fatores de Tempo
12.
Int J Clin Pract ; 58(1): 93-5, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14994979

RESUMO

We present the management of a patient with nasopharyngeal carcinoma with a history of recurrent syncopal attacks diagnosed as malignant vasovagal syndrome. We discuss clinical presentation as well as the resolution of disease symptoms. The importance of metastatic nasopharyngeal malignancy in relation to syncope is discussed.


Assuntos
Neoplasias Nasofaríngeas/complicações , Síncope Vasovagal/etiologia , Idoso , Biópsia por Agulha Fina , Cefaleia/etiologia , Humanos , Masculino , Neoplasias Nasofaríngeas/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
J Neurochem ; 60(6): 2232-7, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8492128

RESUMO

[3H]Adenosine transport was characterized in cerebral cortical synaptoneurosomes prepared from postmortem human brain using an inhibitor-stop/centrifugation method. The adenosine transport inhibitors dipyridamole and dilazep completely and rapidly blocked transmembrane fluxes of [3H]adenosine. For 5-s incubations, two kinetically distinguishable processes were identified, i.e., a high-affinity adenosine transport system with Kt and Vmax values of 89 microM and 0.98 nmol/min/mg of protein, respectively, and a low-affinity adenosine transport system that did not appear to be saturable. For incubations with 1 microM [3H]adenosine as substrate, intrasynaptoneurosomal concentrations of [3H]adenosine were 0.26 microM at 5 s and 1 microM at 600 s. Metabolism of accumulated [3H]adenosine to adenine nucleotides was 15% for 5-s, 23% for 15-s, 34% for 30-s, 43% for 60-s, and 80% for 600-s incubations. The concentrations (microM) of total accumulated 3H-purines ([3H]adenosine plus metabolites) at these times were 0.3, 0.5, 1.0, 1.3 and 5.6, respectively. These results indicate that in the presence of extensive metabolism, the intrasynaptoneurosomal accumulation of 3H-purines was higher than the initial concentration of 1 microM [3H]adenosine in the reaction medium. For 5-, 15-, 30-, 60-, and 600-s incubations in the presence of the adenosine deaminase inhibitor EHNA and the adenosine kinase inhibitor 5'-iodotubercidin, metabolism of the transported [3H]adenosine was 14, 14, 16, 14, and 38%, respectively. During these times, total 3H-purine accumulation was 0.3, 0.5, 0.5, 0.7, and 1.8 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Adenosina/metabolismo , Córtex Cerebral/metabolismo , Sinaptossomos/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Idoso , Transporte Biológico/efeitos dos fármacos , Cadáver , Dilazep/farmacologia , Dipiridamol/farmacologia , Feminino , Humanos , Cinética , Masculino , Sinaptossomos/efeitos dos fármacos , Fatores de Tempo , Trítio , Tubercidina/análogos & derivados , Tubercidina/farmacologia
14.
Hepatology ; 32(3): 556-62, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10960449

RESUMO

We used mice deficient in gamma-glutamyl transpeptidase (GGT) to analyze the effects of GGT deficiency and altered thiol levels on gene expression in liver. GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine, methionine, and cysteinylglycine in liver. Steady-state RNA levels of the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis, are elevated 4-fold in these mice, while those for glutathione synthetase (GSH syn) are elevated 2-fold. RNA levels of cystathionase (cystathionine gamma-lyase), a key enzyme in the synthesis of cysteine from methionine, are elevated approximately 3.5-fold. In contrast, levels of RNA coding for multidrug resistance protein 2 (MRP2), which transports GSH into bile, are half wild-type values. We found no change in RNA levels of enzymes related to oxidative injury (CuZn and Mn superoxide dismutases [SOD], catalase, and glutathione peroxidase). Similarly, RNA levels of glutathione reductase and ribonucleotide reductase were unchanged. Furthermore, in contrast to previous in vitro results, methyl methanesulfonate did not induce stress-activated signal transduction as measured by c-jun phosphorylation in livers of GGT-deficient mice, despite further depletion of GSH by buthionine sulfoximine. Our findings indicate that GGT deficiency itself and/or altered thiol levels regulate expression of genes involved in GSH metabolism, but have no effect on the expression of other antioxidant genes.


Assuntos
Expressão Gênica , Fígado/fisiologia , gama-Glutamiltransferase/deficiência , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Cistationina gama-Liase/genética , Enzimas/metabolismo , Glutationa/biossíntese , Glutationa/metabolismo , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Oxirredutases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA Mensageiro/metabolismo , Estresse Fisiológico/metabolismo , Compostos de Sulfidrila/metabolismo
15.
Lung ; 179(5): 319-30, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11976899

RESUMO

We used mice with a targeted disruption in g-glutamyl transpeptidase (GGT-deficient mice) to study the role of glutathione (GSH) in protection against oxygen-induced lung injury. These mice had reduced levels of lung GSH and restricted ability to synthesize GSH because of low levels of cysteine. When GGT-deficient mice were exposed to 80% oxygen, they developed diffuse pulmonary injury and died within eight days. Ten of 12 wild-type mice were alive after 18 days. Administration of N-acetylcysteine (NAC) to GGT-deficient mice corrected GSH values and prevented the development of severe pulmonary injury and death. Oxygen exposure induced an increase in lung GSH levels in both wild-type and GGT-deficient mice, but induced levels in the mutant mice were <50% of those in wild-type mice. Cysteine levels were approximately 50-fold lower than GSH levels the lungs of both wild-type and GGT-deficient mice. Levels of lung RNA coding for the heavy subunit of g-glutamyl cysteine synthetase rose three- to fourfold after oxygen exposure in both wild-type and GGT-deficient mice. In contrast, oxygen exposure failed to provoke increases in glutathione synthetase, glutathione peroxidase, glutaredoxin, or thioredoxin.


Assuntos
Acetilcisteína/farmacologia , Glutationa/fisiologia , Hiperóxia/metabolismo , Lesão Pulmonar , gama-Glutamiltransferase/deficiência , Animais , Cisteína/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Hiperóxia/etiologia , Pulmão/metabolismo , Camundongos , RNA/genética
16.
J Biol Chem ; 275(43): 33404-8, 2000 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-10938093

RESUMO

Worldwide, millions of people are exposed to arsenic in drinking water that exceeds the World Health Organization standard of 10 microg/liter by as much as 50-300-fold, yet little is known about the molecular basis for arsenic excretion. Here we show that transport of arsenic into bile depends on the MRP2/cMOAT transporter and that glutathione is obligatory for such transport. Using reversed phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic-glutathione complexes not previously identified in vivo, arsenic triglutathione and methylarsenic diglutathione, account for most of the arsenic in the bile. The structure of the compounds was also confirmed by nuclear magnetic resonance spectroscopy. Our findings may help explain the increased susceptibility of malnourished human populations to arsenic.


Assuntos
Arsênio/metabolismo , Arsenicais/metabolismo , Bile/metabolismo , Proteínas de Transporte/fisiologia , Glutationa/análogos & derivados , Glutationa/metabolismo , Animais , Proteínas de Transporte de Ânions , Transporte Biológico , Espectroscopia de Ressonância Magnética , Ratos , Ratos Wistar
17.
Environ Health Perspect ; 107(9): A444-5, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10464082

RESUMO

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165

18.
Proc Natl Acad Sci U S A ; 97(10): 5101-6, 2000 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-10805773

RESUMO

Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-HS(tm1) fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.5. Lethality results from apoptotic cell death rather than reduced cell proliferation. We also isolated cell lines from homozygous mutant blastocysts in medium containing GSH. These cells also grow indefinitely in GSH-free medium supplemented with N-acetylcysteine and have undetectable levels of GSH; further, they show no changes in mitochondrial morphology as judged by electron microscopy. These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth.


Assuntos
Acetilcisteína/farmacologia , Blastocisto/fisiologia , Desenvolvimento Embrionário e Fetal , Glutamato-Cisteína Ligase/metabolismo , Glutationa/biossíntese , Animais , Apoptose , Blastocisto/citologia , Blastocisto/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Morte Fetal , Gástrula/fisiologia , Glutamato-Cisteína Ligase/deficiência , Glutamato-Cisteína Ligase/genética , Glutationa/deficiência , Glutationa/farmacologia , Heterozigoto , Homozigoto , Mesoderma/fisiologia , Camundongos , Camundongos Knockout
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