Structural changes of DNA induced by mono- and binuclear cancer drugs

The structural features of the drug-DNA adducts resulted from treatment of DNA with the platinum based mononuclear drug cisplatin and the binuclear drug [{trans-PtCl(NH3)2}2H2N(CH2)4NH2]Cl2 or bis(platin) have been investigated by atomic force microscopy (AFM). Reduction in the contour length of the DNA fragments has been observed after cisplatin treatment while, compaction and aggregation are found to be the primary structural modifications following treatment with the binuclear drug. The intermolecular interaction upon bis(platin) treatment leads to observation of highly condense aggregates without a distinct sight of single isolated DNA molecule. These differences in drug binding indicate that unlike the mononuclear drug cisplatin, bis(platin) causes extensive interhelical/intermolecular cross-linking through its multiple linking sites. To our knowledge, this is the first report of a comparative AFM study to monitor the effects of a mono- and a binuclear platinum anti-cancer drug on DNA structure. These observations should provide clues towards explaining the distinct biological activities of the two drugs.     

荧光标记法检测不同毒物对细胞骨架的影响

细胞骨架(Cytoskeleton)主要由微管(Microtubule,MT)、微丝(Microfilament,MF)以及中间丝(Intermediate filament,IF)这三种类型组成。它们在细胞的形态维持、物质运输、信号转导、能量转换及细胞的运动和分裂等多个过程中发挥着重要的作用。其中,由肌动蛋白组成的微丝是真核细胞中含量最丰富的一种蛋白复合体,以解聚时的球状肌动蛋白G-actin(Globular actin)或聚合时的纤丝状肌动蛋白F-actin(Filamen-tous actin)形式存在。正常细胞中肌动蛋白两种形态的转换处于动态平衡,共同行使细胞的变形运动、胞质分裂、基质附着和胞间连接等多…     

Morphological and physiological changes in Streptomyces lividans induced by different yeasts

Streptomyces development is a complex process that eventually finishes with the formation of individual unigenomic spores from the aerial hyphae. Intraspecific and interspecific signals must play a key role in triggering or blocking this process. Here we show that interaction between two types of microorganisms, Streptomyces and yeasts, leads to alteration of the Streptomyces developmental program. This alteration is due to the action of invertase produced by the yeast on the sucrose present in the culture media, making glucose and fructose readily available for growth.     

Structural changes in the lungs induced by different levels of hyperbaric oxygenation

Morphological and ultrastructural changes in the lungs of 30 rabbits placed into the altitude chamber with 100% O2 and the pressure of 2, 2.5, 3 and 4 ata for 60 min daily during 1, 2 and 3 weeks have been studied. Morphological changes in the lungs were shown to depend on the degree and duration of oxygen pressure. 2 ata for 60 min daily during two weeks or 2.5 ata for 60 min daily during one week were considered to be safe regimens of hyperbaric oxygenation. Microcirculatory disorders and dystrophic changes of the aero-hematogenic barrier (AHB), its increased permeability, the development of intraalveolar and interstitial edema are observed in the lungs at a higher pressure of 3 or 4 ata. The endothelium and type I alveolocytes are more sensible to high doses of hyperbaric oxygenation. Hydropic degeneration and exfoliation of cells from the basilar membrane are gradually increasing. Type II alveolocytes are more stable to the destructive action of hyperbaric oxygenation. Greater dystrophic changes in other AHB elements are associated with the hypertrophy of mitochondria and lamellar bodies. The described AHB changes are more expressed in atelectasis areas.     

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

Apoptosis plays a central role not only in the physiological processes of kidney growth and remodeling, but also in various human renal diseases and drug-induced nephrotoxicity. We present in a synthetic fashion the main molecular and cellular pathways leading to drug-induced apoptosis in kidney and the mechanisms regulating it. We illustrate them using three main nephrotoxic drugs (cisplatin, gentamicin, and cyclosporine A). We discuss the main regulators and effectors that have emerged as key targets for the design of therapeutic strategies. Novel approaches using gene therapy, antisense strategies, recombinant proteins, or compounds obtained from both classical organic and combinatorial chemistry are examined. Finally, key issues that need to be addressed for the success of apoptosis-based therapies are underlined.     

Regulation of CD2-associated protein influences podocyte endoplasmic reticulum stress-mediated apoptosis induced by albumin overload

The adaptation of microorganisms to pesticide biodegradation relies on the recruitment of catabolic genes by horizontal gene transfer and homologous recombination mediated by insertion sequences (IS). This environment-friendly function is maintained in the degrading population but it has a cost which could diminish its fitness. The loss of genes in the course of evolution being a major mechanism of ecological specialization, we mimicked evolution in vitro by sub-culturing the atrazine-degrading Pseudomonas sp. ADP in a liquid medium containing cyanuric acid as the sole source of nitrogen. After 120 generations, a new population evolved, which replaced the original one. This new population grew faster on cyanuric acid but showed a similar cyanuric acid degrading ability. Plasmid profiles and Southern blot analyses revealed the deletion of a 47 kb region from pADP1 containing the atzABC genes coding for the enzymes that turn atrazine into cyanuric acid. Long PCR and sequencing analyses revealed that this deletion resulted from a homologous recombination between two direct repeats of a 110-bp, identical to ISPps1 of Pseudomonas huttiensis, flanking the deleted 47 kb region. The loss of a region containing three functional genes constitutively expressed thereby constituting a genetic burden under cyanuric acid selection pressure was responsible for the gain in fitness of the new population. It highlights the IS-mediated plasticity of the pesticide-degrading potential and shows that IS not only favours the expansion of the degrading genetic potential thanks to dispersion and duplication events but also contribute to its reduction thanks to deletion events.     

Structural changes in Escherichia coli membranes induced by bacteriophage T4 at different temperatures.

This paper presents some further evidence for our model of DNA translocation into Escherichia coli cells by bacteriophage T4 (see Tarahovsky, Y. S., Khusainov, A. A., Deev, A. A., Kim, Y. V. 1991. FEBS Lett. 289:18-22). When lowering the temperature, we succeeded in slowing down the infection process and in observing a few separate stages by electron microscopy. Also, potassium leakage at different temperatures was measured. At 0-6 degrees C the phage was found to be irreversibly adsorbed on the cell surface, its tail to be contracted, and the outer membrane to be invaginated. Membrane fusion and formation of broad intermembrane bridges with a hole for potassium leakage were shown to start above 7 degrees C. At about 17-20 degrees C the diameter of the bridge decreased considerably, which could correspond to the sealing of the membrane.