Mast Cell Proteoglycans

Mast cells are versatile effector cells of the immune system, contributing to both innate and adaptive immunity toward pathogens but also having profound detrimental activities in the context of inflammatory disease. A hallmark morphological feature of mast cells is their large content of cytoplasmic secretory granules, filled with numerous secretory compounds, including highly negatively charged heparin or chondroitin sulfate proteoglycans of serglycin type. These anionic proteoglycans provide the basis for the strong metachromatic staining properties of mast cells seen when applying various cationic dyes. Functionally, the mast cell proteoglycans have been shown to have an essential role in promoting the storage of other granule-contained compounds, including bioactive monoamines and different mast cell-specific proteases. Moreover, granule proteoglycans have been shown to regulate the enzymatic activities of mast cell proteases and to promote apoptosis. Here, the current knowledge of mast cell proteoglycans is reviewed.     

P-bodies and mitochondria: Which place in RNA interference?

Micro-RNAs (miRNAs) are major actors of RNA interference (RNAi), a regulation pathway which leads to translational repression and/or degradation of specific mRNAs. They provide target specificity by incorporating into the RISC complex and guiding its binding to mRNA. Since the discovery of RNAi, many progresses have been made on the mechanism of action of the RISC complex and on the identification of target mRNAs. However, the regulation of RNAi has been poorly investigated so far. Recently, various studies have revealed physical and functional relationships between RNAi, P-bodies and mitochondria. This review intends to recapitulate these data and discuss their potential importance in cell metabolism.     

应激颗粒的形成与生物学意义

真核细胞对外界压力刺激会做出一系列应答反应,如暂停蛋白质翻译系统,从而使细胞能更好地适应环境压力。通过应激颗粒（stress granules,SG）的形成包裹未被翻译的mRNA是该适应性调节的重要方式。研究表明,环境压力导致eIF2α上游激酶的激活从而磷酸化eIF2α,翻译起始受阻,随后,TIA-1、TTP等蛋白迅速与mRNP结合聚集成SG,并在微管蛋白的帮助下进一步向细胞核聚集,形成成熟的SG。当压力消失,SG依赖微管及其动力蛋白进行解聚,释放包裹的mRNA及蛋白。细胞内成熟的SG在转录后调节中发挥重要作用,并且通过其组成蛋白在肿瘤凋亡、病毒侵染、免疫、炎症反应及由蛋白错误折叠引起的疾病中发挥作用。该文首次综述了压力颗粒研究进展,为充分认识SG的病理生理性调节功能提供参考。     

Herbs in exercise and sports

ABSTRACT: The use of herbs as ergogenic aids in exercise and sport is not novel. Ginseng, caffeine, ma huang (also called 'Chinese ephedra'), ephedrine and a combination of both caffeine and ephedrine are the most popular herbs used in exercise and sports. It is believed that these herbs have an ergogenic effect and thus help to improve physical performance. Numerous studies have been conducted to investigate the effects of these herbs on exercise performance. Recently, researchers have also investigated the effects of Eurycoma longifolia Jack on endurance cycling and running performance. These investigators have reported no significant improvement in either cycling or running endurance after supplementation with this herb. As the number of studies in this area is still small, more studies should be conducted to evaluate and substantiate the effects of this herb on sports and exercise performance. For instance, future research on any herbs should take the following factors into consideration: dosage, supplementation period and a larger sample size.     

Gintonin, a ginseng-derived novel ingredient, evokes long-term potentiation through N-methyl-D-aspartic acid receptor activation: Involvement of LPA receptors

Ginseng has been shown to have memory-improving effects in human. However, little is known about the active components and the molecular mechanisms underlying its effects. Recently, we isolated novel lysophosphatidic acids (LPAs)-ginseng protein complex derived from ginseng, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity. Gintonin activated Ca²⁺-activated Clchannels in Xenopus oocytes through the activation of endogenous LPA receptor. In the present study, we investigated whether the activation of LPA receptor by gintonin is coupled to the regulation of N-methyl-d-aspartic acid (NMDA) receptor channel activity in Xenopus oocytes expressing rat NMDA receptors. The NMDA receptor-mediated ion current (I _NMDA ) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I _NMDA in a concentration-dependent manner. Gintonin-mediated I _NMDA enhancement was blocked by Ki16425, an LPA1/3 receptor antagonist. Gintonin action was blocked by a PLC inhibitor, IP₃ receptor antagonist, Ca²⁺ chelator, and a tyrosine kinase inhibitor. The site-directed mutation of Ser1308 of the NMDA receptor, which is phosphorylated by protein kinase C (PKC), to an Ala residue, or co-expression of receptor protein tyrosine phosphatase with the NMDA receptor attenuated gintonin action. Moreover, gintonin treatment elicited a transient elevation of [Ca²⁺]_i in cultured hippocampal neurons and elevated longterm potentiation (LTP) in both concentration-dependent manners in rat hippocampal slices. Gintonin-mediated LTP induction was abolished by Ki16425. These results indicate that gintonin-mediated I _NMDA potentiation and LTP induction in the hippocampus via the activation of LPA receptor might be responsible for ginseng-mediated improvement of memory-related brain functions.     

Defense response mechanisms of ginseng callus cultures induced by Yersinia pseudotuberculosis, a human pathogen

The effect of Yersinia pseudotuberculosis, the bacterial pathogen affecting humans and animals, on growth of ginseng (Panax ginseng C.A. Mey) cell cultures was studied. The bacteria strongly induced the expression of phenylalanine ammonia-lyase and β-1,3-glucanase, the proteins encoded by the defense-related genes of ginseng and inhibited the normal ginseng callus growth but did not affect the resistant cell cultures. The thermostable and thermolabile protein toxins of these bacteria are lethal to mice when induced parentherally, and they also induced the expression of the defense-related genes in ginseng callus cultures. At the same time, the ginseng cells completely suppressed the bacterial cell growth. These data suggest that the ginseng cells recognized the yersinia and developed the immune response to this pathogen. The interaction between the ginseng cells and Y. pseudotuberculosis is similar to the hypersensitive response of plants to plant pathogens.     

Biodegradation of dimethyl phthalate by Sphingomonas sp. isolated from phthalic-acid-degrading aerobic granules

This study isolated nine strains of aerobic phenol-degrading granules. These isolates (I1–I9) were characterized using 16S rRNA gene sequencing, with γ-Proteobacteria as the dominant strains in the aerobic granules. While most strains demonstrated either high phenol-degrading capabilities or auto-aggregation capabilities, three isolates, I2, I6, and I8 showed both features. These findings contradict the previous view that auto-aggregation and phenol degradation are mutually exclusive in aerobic granules. Strains I2 and I8 independently formed single-culture aerobic granules except for I3. Anti-microbial activity test results indicated that strains I2 and I8 inhibited growth of strain I3. However, co-culturing I3 with I2 or I8 helped to form granules.     

An enzyme family reunion — similarities,differences and eccentricities in actions on <Emphasis Type="Italic">α</Emphasis>-glucans

α-Glucans in general, including starch, glycogen and their derived oligosaccharides are processed by a host of more or less closely related enzymes that represent wide diversity in structure, mechanism, specificity and biological role. Sophisticated three-dimensional structures continue to emerge hand-in-hand with the gaining of novel insight in modes of action. We are witnessing the “test of time” blending with remaining questions and new relationships for these enzymes. Information from both within and outside of ALAMY_3 Symposium will provide examples on what the family contains and outline some future directions. In 2007 a quantum leap crowned the structural biology by the glucansucrase crystal structure. This initiates the disclosure of the mystery on the organisation of the multidomain structure and the “robotics mechanism” of this group of enzymes. The central issue on architecture and domain interplay in multidomain enzymes is also relevant in connection with the recent focus on carbohydrate-binding domains as well as on surface binding sites and their long underrated potential. Other questions include, how different or similar are glycoside hydrolase families 13 and 31 and is the lid finally lifted off the disguise of the starch lyase, also belonging to family 31? Is family 57 holding back secret specificities? Will the different families be sporting new “eccentric” functions, are there new families out there, and why are crystal structures of “simple” enzymes still missing? Indeed new understanding and discovery of biological roles continuously emphasize value of the collections of enzyme models, sequences, and evolutionary trees which will also be enabling advancement in design for useful and novel applications.