Coordination of calcium signalling by endothelial-derived nitric oxide in the intact liver

Calcium ions (Ca2+) and nitric oxide (NO) are key signalling molecules that are implicated in the regulation of numerous cellular processes. Here we show that, in the intact liver, stimulation of endothelial cells by bradykinin coordinates the propagation of vasopressin-dependent intercellular Ca2+ waves across hepatic plates, and markedly increases the frequency of Ca2+ oscillations in individual hepatocytes. Modulation of Ca2+ oscillations by bradykinin is lost following isolation of hepatocytes, but restored in co-cultures of hepatocytes and endothelial cells. The sensitizing effects of bradykinin are mimicked by NO donors and abrogated by NO inhibitors. Thus, crosstalk between NO and Ca2+ signalling pathways through the microvasculature is probably an important mechanism for the coordination of liver function and may have a function in other organs.     

Inhibition of cytochrome P450 isozymes in rat liver microsomes by polysaccharides derived from Phellinus linteus

Polysaccharides (0.5, 1 and 3 mg ml^–1) from cultured broth and mycelia of Phellinus linteus inhibited cytochrome P450 (CYP) 1A1, CYP 1A2, CYP 2B1, and CYP 2E1 activities in rat liver microsomes. The polysaccharides from the broth of Phellinus linteus grown with 5% (v/v) mulberry extract had highest inhibitory potency for CYP 1A1, 1A2 and 2B1 activities. The most potent inhibitor of CYP 2E1 activity were the polysaccharides from the broth of Phellinus linteusgrown with 10% (v/v) mulberry extract.     

Chemopreventive effect of chitosan oligosaccharide against colon carcinogenesis

Chitosan oligosaccharide (COS, 3 kDa相似文献   

Nano-Precision Tweezers for Mechanosensitive Proteins and Beyond

Mechanical forces play pivotal roles in regulating cell shape, function, and fate. Key players that govern the mechanobiological interplay are the mechanosensitive proteins found on cell membranes and in cytoskeleton. Their unique nanomechanics can be interrogated using single-molecule tweezers, which can apply controlled forces to the proteins and simultaneously measure the ensuing structural changes. Breakthroughs in high-resolution tweezers have enabled the routine monitoring of nanometer-scale, millisecond dynamics as a function of force. Undoubtedly, the advancement of structural biology will be further fueled by integrating static atomic-resolution structures and their dynamic changes and interactions observed with the force application techniques. In this minireview, we will introduce the general principles of single-molecule tweezers and their recent applications to the studies of force-bearing proteins, including the synaptic proteins that need to be categorized as mechanosensitive in a broad sense. We anticipate that the impact of nano-precision approaches in mechanobiology research will continue to grow in the future.     

Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences

Akkermansia muciniphila, a mucin-degrading microbe found in the human gut, is often associated with positive health outcomes. The abundance of A. muciniphila is modulated by the presence and accessibility of nutrients, which can be derived from diet or host glycoproteins. In particular, the ability to degrade host mucins, a class of proteins carrying densely O-glycosylated domains, provides a competitive advantage in the sustained colonization of niche mucosal environments. Although A. muciniphila is known to rely on mucins as a carbon and nitrogen source, the enzymatic machinery used by this microbe to process mucins in the gut is not yet fully characterized. Here, we focus on the mucin-selective metalloprotease, Amuc_0627 (AM0627), which is known to cleave between adjacent residues carrying truncated core 1 O-glycans. We showed that this enzyme is capable of degrading purified mucin 2 (MUC2), the major protein component of mucus in the gut. An X-ray crystal structure of AM0627 (1.9 Å resolution) revealed O-glycan–binding residues that are conserved between structurally characterized enzymes from the same family. We further rationalized the substrate cleavage motif using molecular modeling to identify nonconserved glycan-interacting residues. We conclude that mutagenesis of these residues resulted in altered substrate preferences down to the glycan level, providing insight into the structural determinants of O-glycan recognition.     

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.     

Inhibition of polyamine biosynthesis in Acanthamoeba castellanii and 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase activity by chitosanoligosaccharide

Growth of Acanthamoeba castellaniiwas inhibited by chitosanoligosaccharide (up to 20 mg ml^–1) from the shells of crabs but was reversed by the polyamines, putrescine or spermidine, at 0.8 mM. Chitosanoligosaccharide strongly inhibited the induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate, a key enzyme of polyamine biosynthesis, which is enhanced in tumour promotion.     

Biological control as an invasion process: disturbance and propagule pressure affect the invasion success of Lythrum salicaria biological control agents

Understanding the mechanisms behind the successful colonization and establishment of introduced species is important for both preventing the invasion of unwanted species and improving release programs for biological control agents. However, it is often not possible to determine important introduction details, such as date, number of organisms, and introduction location when examining factors affecting invasion success. Here we use biological control introduction data to assess the role of propagule pressure, disturbance, and residence time on invasion success of four herbivorous insect species introduced for the control of the invasive wetland plant, Lythrum salicaria, in the Columbia River Estuary. Two sets of field surveys determined persistence at prior release sites, colonization of new sites, and abundance within colonized sites. We quantified propagule pressure in four ways to examine the effect of different measurements. These included three measurements of introduction size (proximity to introduction site, introduction size at a local scale, and introduction size at a regional scale) and one measure of introduction number (number of introduction events in a region). Disturbance was examined along a tidal inundation gradient (distance from river mouth) and as habitat (island or mainland). Statistical models and model averaging were used to determine which factors were driving invasion success. In this study we found: (1) sparse evidence for the positive influence of propagule pressure on invasion success; (2) disturbance can negatively affect the invasion success of herbivorous insects; (3) the effects of disturbance and propagule pressure are species specific and vary among invasion stages, and (4) not all measures of propagule pressure show the same results, therefore single measures and proxies should be used cautiously.     

Oscillatory Transpiration and Water Uptake of Avena Plants IV. Transpiratory Response to Sine Shaped Light Cycles

The transpiration rate of individual 6-day-old oat plants was forced to oscillate by cyclic sine-shaped changes in the leaf irradiance (frequency 2 cycles h^?1, amplitude and average value 1.4 mW cm^?2, red light 620–800 nm). By means of a specially designed cuvette with three chambers the transpiration rate from three different segments of the leaf could be measured simultaneously. The leaf segments were illuminated individually and the illumination on each leaf segment could be modulated independently. The experiments showed that there was a strong correlation between the transpiration rates from the different leaf segments, dependent on a coupling mechanism in the plant. The coupling phenomenon disappeared when the root system was eliminated or when the water potential of the root medium was lowered. It was experimentally shown that CO₂ diffusion in the leaf could not be the primary cause for the coupling. Therefore the stomatal dependence on the leaf water potential was considered the most probable reason for the coupling. The frequency of the forcing light cycles could be linearly changed during an experiment and this swept-frequency technique was used to obtain a frequency response of one single oat plant. The technique made it also possible to study the strength of the coupling between different leaf segments.