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991.
992.
Debra C. DuBois Zhi-Xin Xu Lorraine McKay Richard R. Almon Nancy Pyszcznski William J. Jusko 《The Journal of steroid biochemistry and molecular biology》1995,54(5-6):237-243
Autoregulation of glucocorticoid receptor (GR) concentration in vivo may be an important determinant of steroid sensitivity. The dynamics of GR regulation were assessed and compared to regulation of tyrosine aminotransferase (TAT) expression in liver tissue taken from rats treated with a single 50 mg/kg i.v. dose of methylprednisolone. Plasma methylprednisolone concentrations were determined by HPLC analysis. Receptor and TAT message levels were determined by quantitative Northern hybridization. Methylprednisolone plasma kinetics showed a half-life of 0.6 h. Receptor occupancy occurred rapidly and cytosolic GR reappeared over 2–12 h. TAT activity rose between 2 and 6 h and then dissipated. Reduction in receptor mRNA levels occurred very rapidly, being detectable by 30 min following steroid administration. A down-regulated steady-state in GR message expression was reached by 2 h post-injection, and was maintained throughout the 18 h examined in this study. Comparison of methylprednisolone kinetics demonstrated that down-regulation was maintained long after drug was eliminated. In contrast, TAT message induction occurred with a sharp peak; maximal induction occurred between 5–6 h and return to baseline at approx. 8–10 h post-induction. This study shows that unlike TAT induction, GR message repression in vivo does not require continual presence of hormone. 相似文献
993.
Giuseppe Satta Lorraine J. Gudas Arthur B. Pardee 《Molecular & general genetics : MGG》1979,168(1):69-80
Summary DNA is more extensively degraded after it is damaged in recA mutants of E. coli than in wild type cells. All data presented here are consistent with the recA gene product, protein X, being an inhibitor of nalidixic acid induced degradation of the bulk DNA (but not of newly replicated DNA). Production of protein X also is correlated with appearance of various S.O.S. repair functions. Evidence was obtained by comparing the rates of protein X synthesis and solubilization of uniformly-labeled DNA in intact cells, incubated in the presence of nalidixic acid. A set of mutants at the lexA locus produced protein X at different rates and degraded their DNA at rates which were inversely correlated to their rates of protein X production. A low concentration of rifampicin quite specifically inhibited protein X production by wild type E. coli, and allowed more rapid DNA degradation. After the DNA was damaged by the incubation of cells in the presence of nalidixic acid, cells preloaded with protein X degraded their DNA more slowly. We propose that protein X could protect DNA against degradation by binding to singlestranded regions, thereby inhibiting nuclease action. 相似文献
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Lorraine C. Backer 《Harmful algae》2009,8(4):618-622
Over the last few decades, scientific research has helped to describe the disease neurotoxic shellfish poisoning (NSP) by identifying the causative organism, Karenia brevis, and by characterizing the disease-causing toxins, a suite of polyether toxins called brevetoxins. In addition to causing disease in exposed human populations, K. brevis blooms and associated management responses have been linked to other effects on coastal communities. Some of these effects are negative, such as the loss of tourism dollars and the increased burden on local health care services caused by increases in human disease incidence. However, some of the effects are positive, such as the significant improvement in detecting brevetoxins in environmental samples and clinical specimens. This review discusses the health and economic effects from K. brevis blooms on Florida coastal communities and the current efforts to identify the data needed to assess social and cultural effects. 相似文献
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999.
Using Moloney murine leukemia virus pseudovirions bearing the envelope protein of Jaagsiekte sheep retrovirus (JSRV), we report here that entry was weakly inhibited by lysosomotropic agents but was profoundly blocked by bafilomycin A1 (BafA1). Kinetics studies revealed that JSRV entry is a slow process and was substantially blocked by a dominant-negative mutant of dynamin. Interestingly, a low-pH pulse overcame the BafA1 block to JSRV infection, although this occurred only if virus-bound cells were preincubated at 37 degrees C, consistent with a very early entry event such as endocytosis being required before the low-pH-dependent step occurs. Moreover, JSRV pseudovirions were resistant to low-pH inactivation. Altogether, this study reveals that JSRV utilizes a pH-dependent, dynamin-associated endocytosis pathway for entry that differs from the classical pH-dependent entry pathway of vesicular stomatitis virus. 相似文献
1000.
IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells 总被引:3,自引:0,他引:3
Jadeski L Mataraza JM Jeong HW Li Z Sacks DB 《The Journal of biological chemistry》2008,283(2):1008-1017
The scaffold protein IQGAP1 integrates signaling pathways and participates in diverse cellular activities. IQGAP1 is overexpressed in a number of human solid neoplasms, but its functional role in tumorigenesis has not been previously evaluated. Here we report that IQGAP1 contributes to neoplastic transformation of human breast epithelial cells. The amount of IQGAP1 in breast carcinoma is greater than that in normal tissue, with highly metastatic breast epithelial cells expressing the highest levels. Overexpression of IQGAP1 enhances proliferation of MCF-7 breast epithelial cells. Reduction of endogenous IQGAP1 by RNA interference impairs both serum-dependent and anchorage-independent growth of MCF-7 cells. Consistent with these in vitro observations, immortalized MCF-7 cells overexpressing IQGAP1 form invasive tumors in immunocompromised mice, whereas tumors derived from MCF-7 cells with stable knockdown of IQGAP1 are smaller and less invasive. In vitro analysis with selected IQGAP1 mutant constructs and a chemical inhibitor suggests that actin, Cdc42/Rac1, and the mitogen-activated protein kinase pathway contribute to the mechanism by which IQGAP1 increases cell invasion. Collectively, our data reveal that IQGAP1 enhances mammary tumorigenesis, suggesting that it may be a target for therapeutic intervention. 相似文献