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151.
Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin 总被引:5,自引:0,他引:5
F Mirabelli A Salis V Marinoni G Finardi G Bellomo H Thor S Orrenius 《Archives of biochemistry and biophysics》1988,264(1):261-269
Incubation of isolated rat hepatocytes with menadione (2-methyl-1,4-naphthoquinone) or the thiol oxidant, diamide (azodicarboxylic acid bis(dimethylamide)), resulted in the appearance of numerous plasma membrane protrusions (blebs) preceding cell death. Analysis of the Triton X-100-insoluble fraction (cytoskeleton) extracted from treated cells revealed a dose- and time-dependent increase in the amount of cytoskeletal protein and a concomitant loss of protein thiols. These changes were associated with the disappearance of actin and formation of large-molecular-weight aggregates, when the cytoskeletal proteins were analyzed by polyacrylamide gel electrophoresis under nonreducing conditions. However, if the cytoskeletal proteins were treated with the thiol reductants, dithiothreitol or beta-mercaptoethanol, no changes in the relative abundance of actin or formation of large-molecular-weight aggregates were detected in the cytoskeletal preparations from treated cells. Moreover, addition of dithiothreitol to menadione- or diamide-treated hepatocytes protected the cells from both the appearance of surface blebs and the occurrence of alterations in cytoskeletal protein composition. Our findings show that oxidative stress induced by the metabolism of menadione in isolated hepatocytes causes cytoskeletal abnormalities, of which protein thiol oxidation seems to be intimately related to the appearance of surface blebs. 相似文献
152.
E. Giavini M. L. Broccia M. Prati D. Bellomo E. Menegola 《In vitro cellular & developmental biology. Animal》1992,28(3):205-210
Summary Rat embryos were explanted on Days 9.5 or 10 of gestation and cultured for 48 to 30h, respectively, in rat serum containing
0, 3, 6, 9 mg/ml of Ethanol (Eth); 0, 10, 20 μg/ml of Acetaldehyde (Ach); 3 mg/ml Eth + 10 μg/ml Ach. At the end of the culture
period the embryos were evaluated for vitality, and scored. Some of them were also examined histologically. Embryos exposed
to Eth from Day 9.5 showed a dose-related growth retardation associated with a high frequency of malformations (open neural
tube, heart defects, branchial arch hypoplasia). The exposure of 9.5-day embryos to 20 μg/ml Ach resulted in 100% embryolethality,
whereas 10 μg/ml induced growth retardation and teratogenic effects. When 10-day embryos were exposed to 3 mg/ml Eth or 10
μl/ml Ach no effects were observed, but the highest levels of Eth produced a moderate growth retardation and morphologic defects.
Exposure to 20 μg/ml Ach induced hypoplasia of the first arch, but did not alter the score value. The histologic examination
of these embryos revealed severe lesions at the level of the neuroepithelium and of the branchial mesenchyma. Similar effects
were observed in embryos exposed simultaneously to 3 mg/ml Eth and 10 μg/ml Ach. These results should make us reevaluate the
role of Ach in the Eth-induced embryopathies. 相似文献
153.
154.
155.
Grapevine field experiments reveal the contribution of genotype,the influence of environment and the effect of their interaction (G×E) on the berry transcriptome
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Silvia Dal Santo Sara Zenoni Marco Sandri Gabriella De Lorenzis Gabriele Magris Emanuele De Paoli Gabriele Di Gaspero Cristian Del Fabbro Michele Morgante Lucio Brancadoro Daniele Grossi Marianna Fasoli Paola Zuccolotto Giovanni Battista Tornielli Mario Pezzotti 《The Plant journal : for cell and molecular biology》2018,93(6):1143-1159
156.
157.
Abstract: Acetylcholine and other muscarinic agonists stimulate the proliferation of rat cortical astrocytes and 132 1N1 human astrocytoma cells by activating muscarinic m3 cholinergic receptors. Ethanol was a potent inhibitor of carbachol-stimulated proliferation, measured by [3 H]thymidine incorporation, with an IC50 of 10 m M . On the other hand, basal and serum-stimulated proliferation of astrocytes and astrocytoma cells was inhibited by ethanol with lower potency (IC50 = 200–250 m M ). Concentration-response experiments with carbachol, in the presence of 10 m M ethanol, suggested that inhibition of proliferation by the alcohol was of the noncompetitive type. Experiments with acetaldehyde and with the alcohol dehydrogenase inhibitor 4-methylpyrazole suggested that the inhibitory effect of alcohol was due to ethanol itself and not to its metabolite acetaldehyde. Proliferation of astrocytoma cells induced by carbachol and the inhibitory effects of ethanol were also confirmed by flow cytometry using the 5-bromodeoxyuridine-Hoechst 33258 method. Ethanol (10 m M ) had no effect on proliferation induced by 50 µg/ml insulin and 100 ng/ml platelet-derived growth factor BB; on the other hand, the mitogenic effect of 1 m M histamine, 100 U/ml interleukin-1, and 100 ng/ml 12- O -tetradecanoylphorbol 13-acetate were inhibited by ∼50%. These results indicate that proliferation of glial cells induced by muscarinic agonists is especially sensitive to the inhibitory effect of ethanol. This action of ethanol may be relevant to its developmental neurotoxicity, particularly microencephaly, which is one of the common features of the fetal alcohol syndrome. 相似文献
158.
Group I pancreatic phospholipase A2 (PLA2 I) is primarily a digestive enzyme. Recently, however, in addition to its catalytic activity a receptor-mediated function has been described for this enzyme. PLA2 I binding to its receptor induces cellular chemokinesis, proliferation, and smooth muscle contraction. This enzyme also induces the production of prostaglandin E2 in certain cells and may have a proinflammatory role. However, despite its ability to hydrolyze phospholipids in in vitro assays, PLA2-I does not efficiently catalyze release of AA from intact cells. Here, we demonstrate that while short-term exposure of NIH 3T3 cells to PLA2-I is ineffective, exposure of 6 h or longer significantly increases the basal release of AA. Dose-response curve of PLA2-I-induced AA release was saturable with an EC50 of 14.01 ± 1.36 nM (n = 3). [3H]-AA was preferentially released over [3H]-oleic acid by PLA2-I, inactivated with 4-bromophenacyl bromide, was fully capable of mediating AA release. These data suggest that a non-catalytic, receptor-mediated mechanism is involved in PLA2-I-induced AA release in NIH-3T3 cells. This relase of AA is not dependent on protein kinase C or Ca2+ concentration. Comparison of the effect of PLA2-I with those of ATP and platelet-derived growth factor indicates that each of these agonists regulates AA release via independent pathways. Neither the basal enzymatic activity of the 85-kDa cytosolic PLA2 nor the protein level of this enzyme was affected by treatment of cells with PLA2-I. However, the increase in basal enzymatic activity of 85 kDa PLA2 due to protein kinase C activation was further enhanced by pretreatment of cells with PLA2-I. We conclude that: (1) short-term exposure of cells to PLA2 I does not cause measurable AA release; (2) release of AA from intact cells by this enzyme requires long-term exposure; (3) AA release is not mediated by a direct catalytic effect of PLA2 I; and (4) AA release by PLA2 I is accomplished via a receptor-mediated process. Taken together, these results raise the possibility that PLA2 I, in addition to its digestive function, may also contribute to aggravate preexisting inflammatory processes and/or to initiate new ones when chronic exposure of cells to this enzyme occurs. © 1995 Wiley-Liss Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
159.
Lucio Tentori Carlo Leonetti Francesco Lozupone Enzo Bonmassar 《Cancer immunology, immunotherapy : CII》1996,41(6):375-383
The antitumor and antimetastatic activity of dacarbazine (DTIC) alone or in combination with cyclophosphamide (CY) was tested in C57BL/6 mice bearing Lewis lung carcinoma (3LL). Treatment with both agents significantly reduced tumor growth and the number of metastases. These effects were associated with marked changes of the biochemical and immunological properties of drug-treated 3LL cells, i.e. (a) reduction of 6 integrin expression, (b) increased susceptibility to natural immunity in vivo, as measured in terms of rapid clearance from mouse lungs of prelabeled 3LL cells injected i.v. and (c) increased immunogenicity, as assessed by T-cell-mediated immune responses (i.e. graft rejection by intact syngeneic mice, and frequency of specific CTL precursors recognizing DTIC/CY-treated cancer cells). The immunotherapeutic advantage afforded by increased immunosensitivity and immunogenicity of 3LL cells exposed to DTIC+CY appears to be markedly reduced in vivo by the profound immunodepressive effects of these drugs. Within this context, addition of interleukin-2 was found to increase the antitumor and antimetastatic activity of this chemotherapeutic regimen. The present study shows, for the first time in a solid tumor model, that a biological response modifier increases the antitumor efficacy of drugs that are able to affect the immunological properties of cancer cells. 相似文献
160.
Gilman B Allen Lucio A Pavone Joseph D DiRocco Jason H T Bates Gary F Nieman 《Journal of applied physiology》2005,99(2):723-730
The mechanical derangements in the acutely injured lung have long been ascribed, in large part, to altered mechanical function at the alveolar level. This has not been directly demonstrated, however, so we investigated the issue in a rat model of overinflation injury. After thoracotomy, rats were mechanically ventilated with either 1) high tidal volume (Vt) or 2) low Vt with periodic deep inflations (DIs). Forced oscillations were used to measure pulmonary impedance every minute, from which elastance (H) and hysteresivity (eta) were derived. Subpleural alveoli were imaged every 15 min using in vivo video microscopy. Cross-sectional areas of individual alveoli were measured at peak inspiration and end exhalation, and the percent change was used as an index of alveolar instability (%I-EDelta). Low Vt never led to an increase in %I-EDelta but did result in progressive atelectasis that coincided with an increase in H but not eta. DI reversed atelectasis due to low Vt, returning H to baseline. %I-EDelta, H, and eta all began to rise by 30 min of high Vt and were not reduced by DI. We conclude that simultaneous increases in both H and eta are reflective of lung injury in the form of alveolar instability, whereas an isolated and reversible increase in H during low Vt reflects merely derecruitment of alveoli. 相似文献