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1.
Am J Respir Cell Mol Biol ; 24(4): 436-41, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11306437

RESUMO

To determine whether overexpression of antioxidant enzymes in lung epithelial cells prevents damage from oxidant injury, stable cell lines were generated with complementary DNAs encoding manganese superoxide dismutase (MnSOD) and/or catalase (CAT). Cell lines overexpressing MnSOD, CAT, or MnSOD + CAT were assessed for tolerance to hyperoxia or paraquat. After exposure to 95% O(2) for 10 d, 44 to 57% of cells overexpressing both MnSOD and CAT and 37 to 47% of cells overexpressing MnSOD alone were viable compared with 7 to 12% of empty vector or parental cells (P < 0.05). To assess if viable cells were capable of cell division after hyperoxic exposures (up to 5 d), a clonogenicity assay was performed. The clonogenic potential of cells overexpressing MnSOD + CAT and MnSOD alone were significantly better than those expressing CAT alone or empty vector controls. In addition, 54 to 72% of cells overexpressing both MnSOD and CAT survived in 1 mM paraquat compared with 58 to 73% with MnSOD alone and 27% with control cells. Overexpression of CAT alone did not improve survival in hyperoxia or paraquat. The combination of MnSOD + CAT did not provide additional protection from paraquat. Data demonstrate that overexpression of MnSOD protects cells from oxidant injury and CAT offers additional protection from hyperoxic injury when co-expressed with MnSOD.


Assuntos
Células Epiteliais/enzimologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Pulmão/citologia , Estresse Oxidativo/fisiologia , Superóxido Dismutase/genética , Catalase/genética , Catalase/metabolismo , Células Epiteliais/citologia , Células HeLa , Herbicidas/farmacologia , Humanos , Hiperóxia/fisiopatologia , Pulmão/metabolismo , Oxidantes/farmacologia , Paraquat/farmacologia , RNA Mensageiro/análise , Superóxido Dismutase/metabolismo , Transgenes/fisiologia
2.
J Biol Chem ; 276(1): 569-75, 2001 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-11034997

RESUMO

It has previously been shown that hyperoxia induces nonapoptotic cell death in cultured lung epithelial cells, whereas hydrogen peroxide (H(2)O(2)) and paraquat cause apoptosis. To test whether pathways leading to oxidative apoptosis in epithelial cells are sensitive to molecular O(2), A549 cells were exposed to 95% O(2) prior to exposure to lethal concentrations of H(2)O(2). The extent of H(2)O(2)-induced apoptosis was significantly reduced in cells preexposed to hyperoxia compared with room-air controls. Preexposure of the hyperoxia-resistant HeLa-80 cell line to 80% O(2) also inhibited oxidant-induced apoptosis, suggesting that this inhibition is not due to O(2) toxicity. Because hyperoxia generates reactive oxygen species and activates the redox-sensitive transcription factor nuclear factor kappa B (NF-kappa B), the role of antioxidant enzymes and NF-kappa B were examined in this inhibitory process. The onset of inhibition appeared to be directly related to the degradation of I kappa B and subsequent activation of NF-kappa B (either by hyperoxia or TNF-alpha), whereas no significant up-regulation of endogenous antioxidant enzyme activities was found. In addition, suppression of NF-kappa B activities by transfecting A549 cells with a dominant-negative mutant construct of I kappa B significantly augmented the extent of H(2)O(2)-induced apoptosis. These data suggest that hyperoxia inhibits oxidant-induced apoptosis and that this inhibition is mediated by NF-kappa B.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Oxidantes/antagonistas & inibidores , Oxigênio/farmacologia , Antioxidantes/metabolismo , Grupo dos Citocromos c/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Citometria de Fluxo , Imunofluorescência , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Quinase I-kappa B , Marcação In Situ das Extremidades Cortadas , Pulmão/metabolismo , NF-kappa B/metabolismo , Oxidantes/farmacologia , Oxigênio/toxicidade , Paraquat/antagonistas & inibidores , Paraquat/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacos , Xantina Oxidase/metabolismo
3.
Mol Genet Metab ; 71(1-2): 359-70, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11001828

RESUMO

Acute lung injury is an unfortunate consequence of oxygen therapy. Increasing evidence suggests that pulmonary dysfunction resulting from acute oxygen toxicity is at least in part due to the injury and death of lung cells. Studies using morphological and biochemical analyses revealed that hyperoxia-induced pulmonary cell death is multimodal, involving not only necrosis, but also apoptosis. A correlative relationship between the severity of hyperoxic acute lung injury and increased apoptosis has been supported by numerous studies in a variety of animal models, although future experiments are necessary to determine whether it is an actual causal relationship. Altered expression of several apoptotic regulatory proteins, such as p53 and Bcl-2, and DNA damage-induced proteins is associated with hyperoxic cell death and lung injury. Stress-responsive proteins, such as heme oxygenase (HO)-1, have been shown to protect animals against hyperoxic cell injury and death. Redox-sensitive transcription factors and mitogen-activated protein kinase signal transduction pathways may play important roles in regulating the expression of stress-responsive and apoptotic regulatory genes. A better understanding of signal transduction pathways leading to hyperoxic cell death may provide new approaches to the treatment of hyperoxia-induced lung injury.


Assuntos
Hiperóxia/metabolismo , Hiperóxia/patologia , Pulmão/metabolismo , Pulmão/patologia , Animais , Apoptose/genética , Morte Celular , Fragmentação do DNA , Regulação da Expressão Gênica , Humanos , Lesão Pulmonar , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Estresse Oxidativo , Oxigênio/toxicidade , Transdução de Sinais , Fatores de Transcrição/metabolismo
4.
Am J Respir Cell Mol Biol ; 22(5): 535-42, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10783124

RESUMO

Hyperoxic lung injury is commonly encountered in patients who require treatment with high concentrations of inspired oxygen. To determine whether interleukin (IL)-6 is protective in oxygen toxicity, we compared the effects of 100% O(2) in transgenic mice that overexpress IL-6 in the lung and transgene (-) controls. IL-6 markedly enhanced survival, with 100% of transgene (-) animals dying within 72 to 96 h, 100% of transgene (+) animals living for more than 8 d and more than 90% of transgene (+) animals living longer than 12 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, and lung lipid peroxidation. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-6 markedly diminished this cytopathic response. The protective effects of IL-6 were not associated with significant alterations in the activities of copper/ zinc superoxide dismutase (SOD) or manganese SOD. They were, however, associated with the enhanced accumulation of the cell-death inhibitor Bcl-2, but not the cell-death stimulator BAX, and with the heightened accumulation of the cell-death regulator tissue inhibitor of metalloproteinase-1 (TIMP-1). These studies demonstrate that IL-6 markedly diminishes hyperoxic lung injury and that this protection is associated with a marked diminution in hyperoxia-induced cell death and DNA fragmentation. They also demonstrate that this protection is not associated with significant alterations in SOD activity, but is associated with the induction of Bcl-2 and TIMP-1.


Assuntos
Hiperóxia/genética , Interleucina-6/genética , Pulmão/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Líquido da Lavagem Broncoalveolar/citologia , Células Cultivadas , Hiperóxia/mortalidade , Marcação In Situ das Extremidades Cortadas , Interleucina-6/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/genética , Pulmão/patologia , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Superóxido Dismutase/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteína X Associada a bcl-2
5.
Antioxid Redox Signal ; 2(1): 103-12, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11232591

RESUMO

Intracellular proteases play an important role in the regulation of apoptosis. A study was performed to determine whether inhibition of the cardiac ATP-dependent ubiquitin 26S protease complex affects cardiomyocyte apoptosis. Isolated rat hearts were perfused for up to 80 min with Krebs-Henseleit buffer +/- the 26S-proteasome inhibitor, MG132 (Z-leu-leu-leucinal). TUNEL-staining of hearts perfused with 25 microM MG132 for 50 min revealed a significant increase (p < 0.05) in the apoptotic index from 1.1% to 15.5% when compared with control hearts perfused with buffer only. Histology of adjacent myocardial sections revealed no signs of necrotic or late apoptotic (nuclear condensation) changes, indicating that the TUNEL-positive nuclei were in the early stages of apoptosis. This early stage of apoptosis was associated with a significant (p < 0.05) reduction in cardiac function. There was a 63% decrease in the rate pressure product in hearts perfused with 25 microM MG132 as compared with a 35% decrease in control hearts over the 80-min perfusion period. Soluble ubiquitin-conjugated proteins, as detected by probing with a specific antibody to ubiquitin, were increased in MG132-treated hearts. In hearts perfused with 50 microM MG132, a greater accumulation of ubiquinated proteins was observed accompanied by a more rapid and greater reduction in hemodynamic function. These observations indicate that prolonged inhibition of the ubiquitin-26S-proteasome results in cardiomyocyte apoptosis accompanied by increased ubiquinated proteins, thus suggesting that accumulation of these abnormal proteins may act as a signal to activate the cell death program.


Assuntos
Apoptose/fisiologia , Proteínas Musculares/metabolismo , Miocárdio/citologia , Processamento de Proteína Pós-Traducional , Ubiquitinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cisteína Endopeptidases , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Leupeptinas/farmacologia , Masculino , Complexos Multienzimáticos/antagonistas & inibidores , Proteínas Musculares/antagonistas & inibidores , Contração Miocárdica/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Complexo de Endopeptidases do Proteassoma , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
6.
Am J Physiol ; 277(3): L589-95, 1999 09.
Artigo em Inglês | MEDLINE | ID: mdl-10484467

RESUMO

We have previously demonstrated that the lungs of mice can exhibit increased programmed cell death or apoptosis after hyperoxic exposure in vivo. In this report, we show that hyperoxic exposure in vitro can also induce apoptosis in cultured murine macrophage cells (RAW 264.7) as assessed by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end-labeling, and nucleosomal assays. To further delineate the signaling pathway of hyperoxia-induced apoptosis in RAW 264.7 macrophages, we first show that hyperoxia can activate the mitogen-activated protein kinase (MAPK) pathway, the extracellular signal-regulated kinases (ERKs) p42/p44, in a time-dependent manner as assessed by increased phosphorylation of ERK1/ERK2 by Western blot analyses. Neither the c-Jun NH(2)-terminal kinase/stress-activated protein kinase nor the p38 MAPK was activated by hyperoxia in these cells. Chemical or genetic inhibition of the ERK p42/p44 MAPK pathway by PD-98059, a selective inhibitor of MAPK kinase, and dominant negative mutants of ERK, respectively, attenuated hyperoxia-induced apoptosis as assessed by DNA laddering and nucleosomal ELISAs. Taken together, our data suggest that hyperoxia can induce apoptosis in cultured murine macrophages and that the MAPK pathway mediates hyperoxia-induced apoptosis.


Assuntos
Apoptose , Hiperóxia/fisiopatologia , Macrófagos/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Animais , Linhagem Celular , Hiperóxia/patologia , Pulmão/patologia , Pulmão/fisiopatologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno , Transdução de Sinais/fisiologia
7.
Am J Physiol ; 276(4): L688-94, 1999 04.
Artigo em Inglês | MEDLINE | ID: mdl-10198367

RESUMO

Findings in recent years strongly suggest that the stress-inducible gene heme oxygenase (HO)-1 plays an important role in protection against oxidative stress. Although the mechanism(s) by which this protection occurs is poorly understood, we hypothesized that the gaseous molecule carbon monoxide (CO), a major by-product of heme catalysis by HO-1, may provide protection against oxidative stress. We demonstrate here that animals exposed to a low concentration of CO exhibit a marked tolerance to lethal concentrations of hyperoxia in vivo. This increased survival was associated with highly significant attenuation of hyperoxia-induced lung injury as assessed by the volume of pleural effusion, protein accumulation in the airways, and histological analysis. The lungs were completely devoid of lung airway and parenchymal inflammation, fibrin deposition, and pulmonary edema in rats exposed to hyperoxia in the presence of a low concentration of CO. Furthermore, exogenous CO completely protected against hyperoxia-induced lung injury in rats in which endogenous HO enzyme activity was inhibited with tin protoporphyrin, a selective inhibitor of HO. Rats exposed to CO also exhibited a marked attenuation of hyperoxia-induced neutrophil infiltration into the airways and total lung apoptotic index. Taken together, our data demonstrate, for the first time, that CO can be therapeutic against oxidative stress such as hyperoxia and highlight possible mechanism(s) by which CO may mediate these protective effects.


Assuntos
Apoptose , Monóxido de Carbono/farmacologia , Heme Oxigenase (Desciclizante)/metabolismo , Hiperóxia/patologia , Hiperóxia/prevenção & controle , Pulmão/patologia , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Heme Oxigenase-1 , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
8.
J Clin Invest ; 103(7): 1047-54, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10194478

RESUMO

Heme oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury. In this study, we examined whether exogenous administration of HO-1 by gene transfer could also confer protection. We first demonstrated the feasibility of overexpressing HO-1 in the lung by gene transfer. A fragment of the rat HO-1 cDNA clone containing the entire coding region was cloned into plasmid pAC-CMVpLpA, and recombinant adenoviruses containing the rat HO-1 cDNA fragment Ad5-HO-1 were generated by homologous recombination. Intratracheal administration of Ad5-HO-1 resulted in a time-dependent increase in expression of HO-1 mRNA and protein in the rat lungs. Increased HO-1 protein expression was detected diffusely in the bronchiolar epithelium of rats receiving Ad5-HO-1, as assessed by immunohistochemical studies. We then examined whether ectopic expression of HO-1 could confer protection against hyperoxia-induced lung injury. Rats receiving Ad5-HO-1, but not AdV-betaGal, a recombinant adenovirus expressing Escherichia coli beta-galactosidase, before exposure to hyperoxia (>99% O2) exhibited marked reduction in lung injury, as assessed by volume of pleural effusion and histological analyses (significant reduction of edema, hemorrhage, and inflammation). In addition, rats receiving Ad5-HO-1 also exhibited increased survivability against hyperoxic stress when compared with rats receiving AdV-betaGal. Expression of the antioxidant enzymes manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (CuZn-SOD) and of L-ferritin and H-ferritin was not affected by Ad5-HO-1 administration. Furthermore, rats treated with Ad5-HO-1 exhibited attenuation of hyperoxia-induced neutrophil inflammation and apoptosis. Taken together, these data suggest the feasibility of high-level HO-1 expression in the rat lung by gene delivery. To our knowledge, we have demonstrated for the first time that HO-1 can provide protection against hyperoxia-induced lung injury in vivo by modulation of neutrophil inflammation and lung apoptosis.


Assuntos
Heme Oxigenase (Desciclizante)/genética , Hiperóxia/fisiopatologia , Pulmão/fisiopatologia , Adenoviridae/genética , Animais , Apoptose/genética , Líquido da Lavagem Broncoalveolar/citologia , Regulação Enzimológica da Expressão Gênica/genética , Técnicas de Transferência de Genes , Heme Oxigenase (Desciclizante)/farmacologia , Heme Oxigenase-1 , Imuno-Histoquímica , Pulmão/metabolismo , Estresse Oxidativo , Oxigênio/toxicidade , Derrame Pleural/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética
9.
Ann N Y Acad Sci ; 887: 164-70, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10668472

RESUMO

Here we discuss the morphological features and our current understanding of the pathways involved in non-apoptotic cell death from O2 toxicity. Preliminary data on hyperoxic signaling indicate that NF-kappa B translocation (and presumptive activation) is not a result of the p42/p44 MAPK pathway, but a likely downstream consequence of activation of the JNK pathway. Our observations suggest the existence of multiple signal transduction pathways in hyperoxia-induced cell death: one involved in the stress response which appears to be NF-kappa B-dependent and another in cell death.


Assuntos
Morte Celular , Oxigênio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Humanos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
10.
Ann N Y Acad Sci ; 887: 171-80, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10668473

RESUMO

Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries. These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents. Simple strategies to mitigate hyperoxia-induced ALI might not be effective by virtue of merely reducing or augmenting the extent of apoptosis of pulmonary cells. Identification of the specific cell types undergoing apoptosis and further understanding of the precise timing of the onset of apoptosis may be necessary in order to gain a greater understanding of the connection between apoptosis and tolerance to hyperoxia and ALI. Attention should also be focused on other forms of non-apoptotic programmed cell death.


Assuntos
Apoptose , Pulmão/patologia , Oxigenoterapia/efeitos adversos , Oxigênio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Humanos , Inflamação , Pulmão/citologia , Pulmão/fisiopatologia , Necrose , Espécies Reativas de Oxigênio , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia
11.
Am J Physiol ; 275(1): L14-20, 1998 07.
Artigo em Inglês | MEDLINE | ID: mdl-9688930

RESUMO

Accumulating evidence demonstrates that genotoxic and oxidant stress can induce programmed cell death or apoptosis in cultured cells. However, little is known about whether oxidative stress resulting from the deleterious effects of hyperoxia can induce apoptosis in vivo and even less is known regarding the functional significance of apoptosis in vivo in response to hyperoxia. Using hyperoxia as a model of oxidant-induced lung injury in the rat, we show that hyperoxic stress results in marked apoptotic signals in the lung. Lung tissue sections obtained from rats exposed to hyperoxia exhibit increased apoptosis in a time-dependent manner by terminal transferase dUTP nick end labeling assays. To examine whether hyperoxia-induced apoptosis in the lung correlated with the extent of lung injury or tolerance (adaptation) to hyperoxia, we investigated the pattern of apoptosis with a rat model of age-dependent tolerance to hyperoxia. We show that apoptosis is associated with increased survival of aged rats to hyperoxia and with decreased levels of lung injury as measured by the volume of pleural effusion, wet-to-dry lung weight, and myeloperoxidase content in aged rats compared with young rats after hyperoxia. We also examined this relationship in an alternate model of tolerance to hyperoxia. Lipopolysaccharide (LPS)-treated young rats not only demonstrated tolerance to hyperoxia but also exhibited a significantly lower apoptotic index compared with saline-treated rats after hyperoxia. To further separate the effects of aging and tolerance, we show that aged rats pretreated with LPS did not exhibit a significant level of tolerance against hyperoxia. Furthermore, similar to the hyperoxia-tolerant LPS-pretreated young rats, the nontolerant LPS-pretreated aged rats also exhibited a significantly reduced apoptotic index compared with aged rats exposed to hyperoxia alone. Taken together, our data suggest that hyperoxia-induced apoptosis in vivo can be modulated by both aging and tolerance effects. We conclude that there is no overall relationship between apoptosis and tolerance.


Assuntos
Envelhecimento/fisiologia , Apoptose , Hiperóxia/patologia , Pulmão/patologia , Animais , Tolerância a Medicamentos , Hiperóxia/fisiopatologia , Imunidade Inata , Lipopolissacarídeos/toxicidade , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Oxigênio/toxicidade , Ratos , Ratos Sprague-Dawley
12.
J Biol Chem ; 272(33): 20646-9, 1997 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9252381

RESUMO

Oxidative insults that are lethal to epithelial cells kill either via apoptosis or necrosis. Nuclear factor-kappaB (NF-kappaB) is a redox-sensitive transcription factor that is activated by oxidative insult, and NF-kappaB activation can protect cells from apoptosis. To test if NF-kappaB can protect from necrotic cell death caused by high levels of molecular O2 (hyperoxia), we exposed human alveolar epithelial (A549) cells to hyperoxia. NF-kappaB was shown to be activated and was translocated to the nucleus within minutes. Nuclear translocation persisted over the course of several days, and the levels of NF-kappaB protein and mRNA increased as well. In hyperoxia, NF-kappaB regulation was independent of mitogen-activated protein kinase (MAPK). In sharp contrast, there was neither nuclear translocation of NF-kappaB nor any increase in expression after exposure to H2O2 at a concentration where this oxidant induces both MAPK and widespread apoptosis. Despite the activation and increased expression of NF-kappaB in hyperoxia, this oxidant remained lethal to the cells. These observations confirm the notion that apoptosis occurs in the absence of NF-kappaB activation but indicate that protection from cell death by NF-kappaB is probably limited to apoptosis.


Assuntos
Apoptose , NF-kappa B/metabolismo , Oxigênio/toxicidade , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , RNA Mensageiro/análise , Células Tumorais Cultivadas
13.
Cell Death Differ ; 4(7): 600-7, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14555973

RESUMO

Apoptosis is a mode of cell death currently thought to occur in the absence of inflammation. In contrast, inflammation follows unscheduled events such as acute tissue injury which results in necrosis, not apoptosis. We examined the relevance of this paradigm in three distinct models of acute lung injury; hyperoxia, oleic acid, and bacterial pneumonia. In every case, it was found that apoptosis is actually a prominent component of the acute and inflammatory phase of injury. Moreover, using strains of mice that are differentially sensitive to hyperoxic lung injury we observed that the percent of apoptotic cells was well correlated with the severity of lung injury. These observations suggest that apoptosis may be one of the biological consequences during acute injury and the failure to remove these apoptotic cells may also contribute to the inflammatory response.

14.
EMBO J ; 13(13): 3211-7, 1994 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8039513

RESUMO

Telomerase is a ribonucleoprotein which synthesizes telomere repeats onto chromosome ends. Telomerase activity is involved in telomere length maintenance. We used Xenopus laevis as a model system to study the expression of telomerase activity in germline cells and during early development. We identified a non-processive telomerase activity in manually dissected nuclei of Xenopus stage VI oocytes. Telomerase activity was detected throughout oogenesis and embryogenesis. Telomerase was active in both S and M phase cell cycle extracts, suggesting that telomerase activity is not regulated with chromosomal DNA replication.


Assuntos
DNA Nucleotidilexotransferase/metabolismo , Oogênese , Óvulo/enzimologia , Espermatozoides/enzimologia , Animais , Sequência de Bases , Núcleo Celular/enzimologia , Primers do DNA , Feminino , Masculino , Mitose , Dados de Sequência Molecular , Fase S , Telômero , Tetrahymena , Xenopus laevis
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