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31.
Paul D. Roepe LiYong Wei Mary M. Hoffman Friederike Fritz 《Journal of bioenergetics and biomembranes》1996,28(6):541-555
Overexpression of the MDR protein, or p-glycoprotein (p-GP), in cells leads to decreased initial rates of accumulation and altered intracellular retention of chemotherapeutic drugs and a variety of other compounds. Thus, increased expression of the protein is related to increased drug resistance. Since several homologues of the MDR protein (CRP, ltpGPA, PDR5, sapABCDF) are also involved in conferring drug resistance phenomena in microorganisms, elucidating the function of the MDR protein at a molecular level will have important general applications. Although MDR protein function has been studied for nearly 20 years, interpretation of most data is complicated by the drug-selection conditions used to create model MDR cell lines. Precisely what level of resistance to particular drugs is conferred by a given amount of MDR protein, as well as a variety of other critical issues, are not yet resolved. Data from a number of laboratories has been gathered in support of at least four different models for the MDR protein. One model is that the protein uses the energy released from ATP hydrolysis to directly translocate drugs out of cells in some fashion. Another is that MDR protein overexpression perturbs electrical membrane potential () and/or intracellular pH (pHi) and therebyindirectly alters translocation and intracellular retention of hydrophobic drugs that are cationic, weakly basic, and/or that react with intracellular targets in a pHi, or -dependent manner. A third model proposes that the protein alternates between drug pump and Cl– channel (or channel regulator) conformations, implying that both direct and indirect mechanisms of altered drug translocation may be catalyzed by MDR protein. A fourth is that the protein acts as an ATP channel. Our recent work has tested predictions of these models via kinetic analysis of drug transport and single-cell photometry analysis of pHi, , and volume regulation in novel MDR and CFTR transfectants that have not been exposed to chemotherapeutic drugs prior to analysis. This paper reviews these data and previous work from other laboratories, as well as relevant transport physiology concepts, and summarizes how they either support or contradict the different models for MDR protein function. 相似文献
32.
利用人粒细胞集落刺激因子(hG-CSF)cDNA3′端非翻译区(3′-UTR)中存在的DraⅠ酶切位点,通过部分酶切与完全酶切,删除3′-UTR不同长度,构建了四种hG-CSFcDNA瞬时重组表达质粒。转染COS-7细胞后,生物活性测定结果提示,hG-CSFcDNA3′-UTR对其表达起负调控作用,其关键性序列位于紧接终止密码子TGA下游的65bp范围内,3′-UTR对hG-CSFcDNA表达的影响与转录水平的差别有一定关系。 相似文献
33.
We describe a new immunoassay which combines an immunosorbent assay, Immunogold silver staining and epipolarization microscopy. Our new assay procedure features multiple samples on a single microscope slide, and high sensitivity of epipolarization microscope for detection of silver-enhanced colloidal gold as a final immunoassay product. We call the new immunoassay “on slide immunogold assay” (OSIGA). This new method uses biotinylated antibody and streptavidin-gold reaction with silver enhancement technique. With OSIGA it is possible to investigate 30 samples on a single microscopic slide. Our preliminary studies used 10-20 μ1 samples and detected nanogram quantities of a standardized protein solution. Unlike enzyme linked immunosorbent assay (ELISA), which has a limited time for reading the final color products, the OSIGA specimens can be dried or resin mounted for longer storage and future reference. 相似文献
34.
All-trans retinoic acid is well known as a modulator of positional specification in vertebrate development. A similar mechanism may operate in molluscan development. Molluscan development is characterized by an invariant pattern of cell divisions, which allows the study of individual cells in the developing organism. Low concentrations of exogenous retinoic acid applied during gastrulation affect the cell division pattern in the early larval stage of the molluscLymnaea stagnalis. A few cells from the apical plate, a larval organ consisting of seven large cleavage-arrested cells, were induced by retinoic acid to resume cell division. They typically formed an area of proliferating small cells that resembles the adjacent areas of precursor cells of adult ectoderm. The identification of individual cells that are transformed by retinoic acid may provide new insights into the mechanisms underlying positional specification within the embryo. 相似文献
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比较研究几种兼性和专一性CAM植物材料的PEPC同工酶表明:经自然干旱诱导,兼性CAM植物露花(Mesembryanthemumcordifolium)、长药景天(Sudumspectabile)有新的PEPC同工酶的出现,诱导前后各同工酶的天然分子量变化不大;而土三七(Sedumaizoon)则没有新的PEPC同工酶出现,但诱导后其同工酶的天然分子量有所增大。以上几种兼性CAM植物的PEPC同工酶酶谱无明显昼夜变化。专一性CAM植物的PEPC酶谱和天然分子量均较一致,亦无昼夜差异。 相似文献
38.
腹腔注射链脲佐霉素(65mg/kg)诱发Wistar大鼠糖尿病。糖尿病发病4周后,向饲料中加尼群地平(30mg·kg-1·d-1)。结果表明,糖尿病4周时大鼠心室舒张功能首先受损,8周后心室舒张和收缩功能均明显受累。尼群地平处理对糖尿病大鼠的心肌收缩性有一定的改善作用。提示尼群地平对大鼠糖尿病性心肌病有一定有益作用。 相似文献
39.
Through simple model analysis, the mass action kinetic model for lipolytic enzymes in biphasic aqueous-organic systems can be simplified using the quasi-steady state assumption (or the quasi-equilibrium state assumption) for the adsorbed enzyme E* or the enzyme-substrate complex E*S. Some parameter combinations leading to the above assumptions are derived confirmed by full numerical integration of the whole enzymatic process. The results may be classified into three categories: (1) the quasi-equilibrium state assumption for E*, (2) the quasi-steady state assumption for E*, and (3) the quasi-steady state assumption for E*S. Further simplification for both E* and E*S is also discussed. (c) 1993 Wiley & Sons, Inc. 相似文献
40.
Ziliang Li Weijie Xu Luyao Kang Yakov Kuzyakov Leiyi Chen Mei He Futing Liu Dianye Zhang Wei Zhou Xuning Liu Yuanhe Yang 《Global Change Biology》2023,29(22):6367-6382
Mineralization of dissolved organic matter (DOM) in thermokarst lakes plays a non-negligible role in the permafrost carbon (C) cycle, but remains poorly understood due to its complex interactions with external C and nutrient inputs (i.e., aquatic priming and nutrient effects). Based on large-scale lake sampling and laboratory incubations, in combination with 13C-stable-isotope labeling, optical spectroscopy, and high-throughput sequencing, we examined large-scale patterns and dominant drivers of priming and nutrient effects of DOM biodegradation across 30 thermokarst lakes along a 1100-km transect on the Tibetan Plateau. We observed that labile C and phosphorus (P) rather than nitrogen (N) inputs stimulated DOM biodegradation, with the priming and P effects being 172% and 451% over unamended control, respectively. We also detected significant interactive effects of labile C and nutrient supply on DOM biodegradation, with the combined labile C and nutrient additions inducing stronger microbial mineralization than C or nutrient treatment alone, illustrating that microbial activity in alpine thermokarst lakes is co-limited by both C and nutrients. We further found that the aquatic priming was mainly driven by DOM quality, with the priming intensity increasing with DOM recalcitrance, reflecting the limitation of external C as energy sources for microbial activity. Greater priming intensity was also associated with higher community-level ribosomal RNA gene operon (rrn) copy number and bacterial diversity as well as increased background soluble reactive P concentration. In contrast, the P effect decreased with DOM recalcitrance as well as with background soluble reactive P and ammonium concentrations, revealing the declining importance of P availability in mediating DOM biodegradation with enhanced C limitation but reduced nutrient limitation. Overall, the stimulation of external C and P inputs on DOM biodegradation in thermokarst lakes would amplify C-climate feedback in this alpine permafrost region. 相似文献