PS externalization: from corpse clearance to drug delivery.
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Annexin A5↗
Biomedical subjects
D Xue
Publications and source records attributed to D Xue.
Mitochondrial endonuclease G is important for apoptosis in C. elegans.
Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dying cells and their nuclei shrink and fragment and the chromosomal DNA is degraded into internucleosomal repeats. Here we report the characterization of the cps-6 gene, which appears to function downstream of, or in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the DNA degradation process during apoptosis. cps-6 encodes a homologue of human mitochondrial endonuclease G, and its protein product similarly localizes to mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans. This observation provides in vivo evidence that the DNA degradation process is important for proper progression of apoptosis. CPS-6 is the first mitochondrial protein identified to be involved in programmed cell death in C. elegans, underscoring the conserved and important role of mitochondria in the execution of apoptosis.
Amino Acid Sequence↗
Regional characteristics of sulfur and lead isotope ratios in the atmosphere at several Chinese urban sites.
Sulfur and lead isotope ratios in the atmosphere were measured at several selected sites (Harbin, Changchun, Dalian, Waliguan, Shanghai, Nanjing, Guiyang) in China and Tsukuba (Japan), to reveal regional sources characteristics over Eastern Asia. Average S isotope ratios for SO2 and sulfate in the atmosphere in China were close to those of the coals used in each region, indicating a considerable contribution of coal combustion to the sulfur compounds in the atmosphere. Most northern cities had around 5% sulfur isotope ratio, while Guiyang, a southwestern city in China, showed a considerably lower sulfur isotope ratio (about -3%) because of the unusually light sulfur isotope ratio of coals in this region. These were considerably different from the value (-1.4%) for Tsukuba (Japan). Lead isotope ratios also suggested that coal combustion considerably contributed to atmospheric lead in some cases in China. At the same time, influences by the emission of Chinese lead ores were also observed in northern cities. Seasonal variations of both sulfur and lead isotope ratios indicated the existence of a certain amount of industrial sources other than coal combustion. In addition, fractionation effect between SO2 and sulfate showed a seasonal tendency (high in winter (0-6%) and low in summer (-1-3%)), suggesting the oxidation pathway of SO2 changed seasonally.
Air Pollution↗
Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin's oxygen affinity.
The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln(3+) binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non-cooperative weak sites (N(W)) with binding constants in decreasing order: K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln(3+) concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln(3+) binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2, the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+) concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This was indicated by the changes in secondary structure characterized by the decrease of alpha-helix content.
2,3-Diphosphoglycerate↗
If phosphatidylserine is the death knell, a new phosphatidylserine-specific receptor is the bellringer.
Recognition of phosphatidylserine (PtdSer) is essential for engulfment of apoptotic cells by mammalian phagocytes. Engagement of a new phosphatidylserine-specific receptor (PtdSerR) appears to be necessary for uptake of apoptotic cells. Many other mammalian receptors have been described to function in the clearance of apoptotic cells. The emerging picture is that many of these receptors may provide the strong adhesion needed to increase the likelihood of contact between the PtdSerR and its phospholipid ligand, which is required for uptake. Furthermore, stimulation of this receptor on different types of phagocytes by apoptotic cells, PtdSer-containing liposomes or an IgM monoclonal anti-PtdSer antibody initiates release of TGFbeta, known to be involved in the anti-inflammatory effects of apoptotic cells. Although highly homologous genes exist in C. elegans and Drosophila melanogaster, their role in engulfment of apoptotic cells remains to be determined.
Animals↗
Long-term results of ammonia removal and transformation by biofiltration.
In this paper, long-term (>8 month) results of ammonia removal in biofilters was studied. Compost was used as the biofilter medium and activated carbon as an added material. The ammonia removal was normally >95% at influent ammonia concentrations of 20-500ppmv. According to the test results, the influent ammonia concentration should be <200ppmv (0.1570g ammonia/kg media per day) so that the effluent concentration of ammonia is <1.0mg/m(3) (the emission standard of China), and the biofiltration system can achieve good long-term performance. In the biofiltration system utilized in this study, the shortest retention time that the system could attain was 0.532min. However, the retention time can be decreased further without decreasing the ammonia removal efficiency. Countercurrent flow is favorable, as it enhances the moisture retention ability of the media. In the bioreactors, ammonia can be converted into the nitrate. The bioreactors have a stratification phenomenon for ammonia removal over the biofiltration depth, which implies that different parts of the bioreactor play different roles in the ammonia removing process.
Air Pollution↗
Demonstration of the in vivo interaction of key cell death regulators by structure-based design of second-site suppressors.
Demonstrating in vivo interaction of two important biomolecules and the relevance of the interaction to a biological process have been difficult issues in biomedical research. Here, we report the use of a homology modeling approach to establish the significance of protein interactions in governing the activation of programmed cell death in Caenorhabditis elegans. A protein interaction cascade has been postulated to mediate activation of cell death in nematodes, in which the BH3-domain-containing (Bcl-2 homology region 3) protein EGL-1 binds the cell-death inhibitor CED-9 and induces release of the death-activating protein CED-4 from inhibitory CED-4/CED-9 complexes. We show here that an unusual gain-of-function mutation in ced-9 (substitution of glycine 169 to glutamate) that results in potent inhibition of most nematode cell deaths impairs the binding of EGL-1 to CED-9 and EGL-1-induced release of CED-4 from CED-4/CED-9 complexes. Based on a modeled EGL-1/CED-9 complex structure, we generated second-site compensatory mutations in EGL-1 that partially restore the binding of EGL-1 to CED-9(G169E) and EGL-1-induced release of CED-4 from CED-4/CED-9(G169E) complexes. Importantly, these mutations also significantly suppress the death-protective activity of CED-9(G169E) in vivo. These results establish that direct physical interaction between EGL-1 and CED-9 is essential for the release of CED-4 and the activation of cell death. The structure-based design of second-site suppressors via homology modeling should be widely applicable for probing important molecular interactions that are implicated in fundamental biological processes.
Amino Acid Sequence↗
U snRNP assembly in yeast involves the La protein.
In all eukaryotic nuclei, the La autoantigen binds nascent RNA polymerase III transcripts, stabilizing these RNAs against exonucleases. Here we report that the La protein also functions in the assembly of certain RNA polymerase II-transcribed RNAs into RNPs. A mutation in a core protein of the spliceosomal snRNPs, Smd1p, causes yeast cells to require the La protein Lhp1p for growth at low temperatures. Precursors to U1, U2, U4 and U5 RNAs are bound by Lhp1p in both wild-type and mutant cells. At the permissive temperature, smd1-1 cells contain higher levels of stable U1 and U5 snRNPs when Lhp1p is present. At low temperatures, Lhp1p becomes essential for the accumulation of U4/U6 snRNPs and for cell viability. When U4 RNA is added to extracts, the pre-U4 RNA, but not the mature RNA, is bound by Smd1p. These results suggest that, by stabilizing a 3'-extended form of U4 RNA, Lhp1p facilitates efficient Sm protein binding, thus assisting formation of the U4/U6 snRNP.
Base Sequence↗
Preliminary study on the relationship between cAMP level and gsp expression in cultured human pituitary somatotrophinomas.
In order to investigate the relationship between abnormal intracellular signal transduction and tumorgenesis of human pituitary somatotrophinomas, the effects of protein kinase A (PKA)-dependent growth hormone (GH) releasing hormone (GHRH) and protein kinase C (PKC)-dependent GH-releasing peptide (GHRP-6) on cAMP production were observed by using cell culture and biochemical methods, and the expression of the gsp oncogene was detected by using PCR and direct sequence assay methods in 11 patients with human pituitary somatotrophinomas. It was found that GHRP-6 exerted significant stimulatory effect on cAMP production by 2 gsp-positive tumors and no effect on the gsp-negative tumors. GHRP-6 could enhance the stimulation of cAMP production induced by GHRH in tumor without gsp oncogenes. It was suggested that both GHRH and GHRP-6 exert identical effects on human pituitary soamtotrophinomas, which was contributed to the cross-talk between the two intracellular signal transduction pathways in pituitary cells.
Adenoma↗
The regulatory effects of protein kinase C on the proliferation of cultured human low-passage meningioma cells.
The potential role of the protein kinase C (PKC)-mediated signal transduction pathways in growth regulation was evaluated and the effects and the possible mechanism of PKC inhibitor on low-passage human meningioma cells in vitro investigated. Freshly resected meningiomas obtained from the operation were placed into cell cultures. Cells from early-passage were used for the following experiments. The numbers of the cultured meningioma cells were counted to evaluate the effect of the PKC inhibitor staurosporine on proliferation of meningioma cells. The basal phosphatidylinositol (PI) turnover rate and the inhibitory rate of starosporine on the proliferation of the meningioma cells were detected. It was found that the proliferation of the low-passage human meningioma cells was inhibited by staurosporine in a dose-dependent manner. The inhibitory rate of staurosporine was positively correlated with the basal PI turnover rate (r = 0.58, P < 0.01). It was suggested that PKC-mediated signal pathway is involved in the proliferation of the low-passage human meningioma cells. The procedure that PKC regulated the proliferation of human meningioma cells is a complex procedure. It is necessary to make more research in order to explore a non-operation therapy or an adjuvant therapy.
Cell Division↗
The role of protein kinase C and its effect on GHRH in the regulation of hormone secretion by somatotrophinomas.
Phorbol ester-induced release of growth hormone (GH) and prolactin (PRL) from human somatotrophic tumors was examined in vitro. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) strongly stimulated GH and PRL secretion and showed an additive effect on GH secretion if used in combination with GH releasing hormone (GHRH). In contrast, staurosporine exerted a variable inhibitory effect on GH release. There was no correlation between such effects and gsp mutations. The findings suggested that TPA doesn't act directly through cAMP signal transduction system.
GTP-Binding Protein alpha Subunits, Gs↗
Analysis of programmed cell death in the nematode Caenorhabditis elegans.
The nematode Caenorhabditis elegans has been shown to be an excellent model organism with which to study the mechanisms of programmed cell death because of its powerful genetics and the ability to study cell death with single-cell resolution. In this chapter, we describe methods that are commonly used to examine various aspects of programmed cell death in C. elegans. These methods, in combination with genetic analyses, have helped identify and characterize many components of the C. elegans cell death pathway, illuminating the mechanisms by which these components affect programmed cell death.
Animals↗
Preoperative anaplastic glioma tumor volume effects on patient survival.
BACKGROUND AND OBJECTIVES: The relationship between preoperative tumor volume and patient survival has long been studied, but the results have been inconsistent. Since geometric measurement of tumor volume was used in these studies, the aim of this study was to ascertain whether the inconsistency of the study results is due to less accurate geometric measurement. METHODS: Prognostic tumor volume effects were compared between the planimetry method and the geometric method using survival analysis, performed for 99 patients diagnosed with anaplastic glioma tumor. RESULTS: A significant correlation was found between planimetry tumor volume and patient survival, but there was no correlation between geometric tumor volume and patient survival. The larger planimetry tumor volume was significantly associated with shorter survival. CONCLUSIONS: The study indicated that in brain tumor research the preoperative tumor volume measured by the geometric method may not be prognostically important. The more accurate measurement, i.e., the planimetry method (based on either computed tomography or magnetic resonance imaging), is needed in brain tumor clinical research and prognostic diagnosis.
Adult↗
TPA enhances growth hormone (GH) secretion effect of GH-releasing hormone (GHRH) by human gsp-positive pituitary somatotrophinomas.
In recent years, one of the most exciting advances in the researches of pituitary adenomas is the discovery that 30%-40% of human pituitary somatotrophinomas carry somatic mutations of the gene for the alpha-subunit of the stimulatory GTP-binding protein, Gs (Gs alpha). These mutations, termed gsp oncogenes, may play an important role in the tumorigenesis of pituitary adenomas. Of 10 somatotrophinomas examined, 3 (30%) were proved to be gsp positive, as determined by sequence analysis of DNA generated by the polymerase chain reaction (PCR). GHRH exerted a significant stimulatory effect on GH secretion in 2 of 3 gsp-positive and 4 of 7 gsp-negative tumors. Moreover, phorbol ester, 1, 2-tetradecanoylphorbol-13-acetate (TPA), enhanced stimulation of lated the GH secretion effect exerted by GHRH in gsp-positive somatotrophinomas, whereas this effect was not observed in gsp-negative tumors. This result suggests that the protein kinase C signal system as well as adenylyl cyclase-cAMP-protein kinase A intracellular signal transduction system plays a pivotal role in GH secretory control of GHRH, which may work together via a cross-talk mechanism.
Adenoma↗
Microcomputer-based technique for 3-D reconstruction and volume measurement of computed tomographic images. Comparison of geometric and planimetry post-operative tumor volume effects on patient survival.
The relationship between brain tumor size and survival has been studied since the advent of CT and magnetic resonance imaging (MRI), however, all published studies are based on tumor sizes measured by the less accurate geometric method, with results that are inconsistent. For example, the influence of the extent of tumor resection on patient survival has been debated. Jelsma and Bucy advocated extensive resection based on their analysis of patients with glioblastoma multiforme, however, Green et al. produced conflicting results, showing that the extent of resection was not statistically significant when all variables were considered simultaneously. The present study investigates whether or not the study inconsistency is largely due to the use of the less accurate geometric tumor volume measurement. The study demonstrates that the geometric tumor volume and the planimetry tumor volume have significantly different prognostic effects.
Adult↗
Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia.
OBJECTIVE: Tracer constants (Ki) for blood-to-brain diffusion of sucrose were measured in the rat to profile the time course of blood-brain barrier injury after temporary focal ischemia, and to determine the influence of post-ischemic hypothermia. METHODS: Spontaneously hypertensive rats were subjected to transient (2 hours) clip occlusion of the right middle cerebral artery. Reperfusion times ranged from 1.5 min to 46 hours, and i.v. 3H-sucrose was circulated for 30 min prior to each time point (1 h, 4 h, 22 h, and 46 h; n = 5-7 per time point). Ki was calculated from the ratio of parenchymal tracer uptake and the time-integrated plasma concentration. Additional groups of rats (n = 7-8) were maintained either normothermic (37.5 degrees C) or hypothermic (32.5 degrees C or 28.5 degrees C) for the first 6 hours of reperfusion, and Ki was measured at 46 hours. RESULTS: Rats injected after 1.5-2 min exhibited a 10-fold increase in Ki for cortical regions supplied by the right middle cerebral artery (p < 0.01). This barrier opening had closed within 1 to 4 hours post-reperfusion. By 22 hours, the blood-brain barrier had re-opened, with further opening 22 and 46 hours (p < 0.01), resulting in edema. Whole body hypothermia (28 degrees C-29 degrees C) during the first six hours of reperfusion prevented opening, reducing Ki by over 50% (p < 0.05). CONCLUSIONS: Transient middle cerebral artery occlusion evokes a marked biphasic opening of the cortical blood-brain barrier, the second phase of which causes vasogenic edema. Hypothermic treatment reduced infarct volume and the late opening of the blood-brain barrier. This opening of the blood-brain barrier may enhance delivery of low permeability neuroprotective agents.
Animals↗
Studies on the cytosolic phospholipase A2 in immortalized astrocytes (DITNC) revealed new properties of the calcium ionophore, A23187.
Besides playing an important role in the maintenance of cell membrane phospholipids, phospholipases A2 (PLA2) are responsible for the release of arachidonic acid (AA) which is a precursor for prostaglandin biosynthesis. The cytosolic PLA2 has been the focus of recent studies, probably due to its ability to respond to protein kinases and changes in intracellular calcium levels. In this study, we examined agents for stimulation of the cytosolic phospholipase A2 in immortalized astrocytes (DITNC). Incubation of DITNC cells with [14C]arachidonic acid (AA) resulted in a time-dependent uptake of the label into phospholipids (PL) and neutral glycerides. In prelabeled cells, release of labeled AA could be stimulated by calcium mobilizing agents such as calcium ionophore A23187 (4-20 microM) and thimerosal (100 microM), and by phorbol myristate acetate (PMA, 100 nM), an agent for activation of protein kinase C. The release of AA could also be stimulated by ATP (200 microM), probably through activation of the purinergic receptor but not by glutamate (1 mM). The stimulated release of AA was dependent on extracellular Ca2+ and was inhibited by mepacrine (50 microM), a non-specific PLA2 inhibitor. Western blot analysis further confirmed the presence of an 85 kDa cPLA2 in both membrane and cytosol fractions of these cells and stimulation by A23187 resulted in translocation of this protein to the membrane fraction. Besides labeled fatty acids, A23187 also stimulated the concomitant release of labeled PL into the culture medium and this event was accompanied by the increased release in lactate dehydrogenase (LDH). Results thus revealed that besides activation of cPLA2, the calcium ionophore A23187 is capable of perturbating cell membrane integrity.
Animals↗
A role for the yeast La protein in U6 snRNP assembly: evidence that the La protein is a molecular chaperone for RNA polymerase III transcripts.
The first protein that binds to all newly synthesized RNA polymerase III transcripts is a highly conserved phosphoprotein known as the La autoantigen. Although binding by the yeast La protein Lhp1p to pre-tRNAs is required for the normal pathway of tRNA maturation, the role of the La protein in the biogenesis of other polymerase III transcripts has been unclear. We identified a mutation in a novel component of the U6 snRNP that causes yeast cells to require Lhp1p for growth. This protein, Lsm8p, is a member of a family of proteins, known as Sm-like proteins, that shares two conserved motifs with the core Sm proteins of the U1, U2, U4 and U5 snRNPs. The lsm8-1 cells have drastically reduced levels of the mature U6 snRNP, consistent with a defect in U6 snRNP assembly. In these cells, Lhp1p stabilizes newly synthesized U6 RNA, thus facilitating assembly of the RNA into the U6 snRNP. These results provide evidence that Lhp1p is a molecular chaperone for polymerase III-transcribed RNAs and implicate Lsm8p as a key component in the very early steps of U6 snRNP assembly.
Amino Acid Sequence↗