Dual mechanisms of Bcl-2 regulation in IP_(3)-receptor-mediated Ca^(2+)release:A computational study

Inositol 1,4,5-trisphosphate receptors(IP_(3)R)-mediated calcium ion(Ca^(2+))release plays a central role in the regulation of cell survival and death.Bcl-2 limits the Ca^(2+)release function of the IP3R through a direct or indirect mechanism.However,the two mechanisms are overwhelmingly complex and not completely understood.Here,we convert the mechanisms into a set of ordinary differential equations.We firstly simulate the time evolution of Ca^(2+)concentration under two different levels of Bcl-2 for the direct and indirect mechanism models and compare them with experimental results available in the literature.Secondly,we employ one-and two-parameter bifurcation analysis to demonstrate that Bcl-2 can suppress Ca^(2+)signal from a global point of view both in the direct and indirect mechanism models.We then use mathematical analysis to clarify that the indirect mechanism is more efficient than the direct mechanism in repressing Ca^(2+)signal.Lastly,we predict that the two mechanisms restrict Ca^(2+)signal synergistically.Together,our study provides theoretical insights into Bcl-2 regulation in IP_(3)R-mediated Ca^(2+)release,which may be instrumental for the successful development of therapies to target Bcl-2 for cancer treatment.

The fertilization-induced Ca^(2+) oscillation in mouse oocytes is cytoplasmic maturation dependent

Mature eggs (at metaphase Ⅱ stage) produce a series of Ca2+ oscillation at fertilization. To define whether the fertilization-induced Ca2+ oscillation is restrict to the metaphase Ⅱ eggs and cell cycle dependent, mouse oocytes at prophase Ⅰ (arrested at germinal vesicle stage),metaphase Ⅰ, metaphase Ⅱ, as well as the pronuclear embryos at interphase of the first mitotic division derived from fertilization or parthenogenetic activation were inseminated after removal of zona pellucida. The results show that the fertilization-induced Ca2+ oscillation is not specific to metaphase Ⅱ eggs. This is supported by the fact that immature oocytes generated the Ca2+ oscillations at fertilization regardless of their nuclear progression from prophase Ⅰ to metaphase Ⅰ (in vitro matured) stage. More interestingly, it was first found that pronuclear embryos at interphase derived from parthenogenetic activation showed Ca2+ oscillations in response to fertilization while the zygotes at interphase did not after reinsemination or intracytoplasmic injection of sperm extracts which induce Ca2+ oscillations in MII eggs. This suggests that the ability of oocytes to generate Ca2+ oscillation in response to sperm penetration is not regulated in a cell cycle dependent manner but dependent on the cytoplasmic maturation.

Regulation Mechanisms of Stomatal Oscillation

Stomata function as the gates between the plant and the atmospheric environment. Stomatal movement, including stomatal opening and closing, controls CO2 absorption as the raw material for photosynthesis and water loss through transpiration. How to reduce water loss and maintain enough CO2 absorption has been an interesting research topic for some time. Simple stomatal opening may elevate CO2 absorption, but, in the meantime, promote the water loss, whereas simple closing of stomatal pores may reduce both water loss and CO2 absorption, resulting in impairment of plant photosynthesis. Both processes are not economical to the plant. As a special rhythmic stomatal movement that usually occurs at smaller stomatal apertures, stomatal oscillation can keep CO2 absorption at a sufficient level and reduce water loss at the same time, suggesting a potential improvement in water use efficiency. Stomatal oscillation is usually found after a sudden change in one environmental factor in relatively constant environments. Many environmental stimuli can induce stomatal oscillation. It appears that, at the physiological level, feedback controls are involved in stomatal oscillation. At the cellular level, possibly two different patterns exist： （i） a quicker responsive pattern; and （ii） a slower response. Both involve water potential changes and water channel regulation, but the mechanisms of regulation of the two patterns are different. Some evidence suggests that the regulation of water channels may play a vital and primary role in stomatal oscillation. The present review summarizes studies on stomatal oscillation and concludes with some discussion regarding the mechanisms of regulation of stomatal oscillation.

基因表达的钙离子调控机制研究

基于基因调节系统的动力学模型,利用数值模拟方法研究了Ca2+振荡对基因表达活性的影响.结果表明:细胞内Ca2+振荡能降低活化转录因子的有效钙阈值;转录因子的活性随Ca2+浓度平均水平增高而增大,但随着细胞内Ca2+振荡周期的增大而减小.

Water Channels Are Involved in Stomatal Oscillations Encoded by Parameter-Specific Cytosolic Calcium Oscillations

Earlier studies have shown that various stimuli can induce specific cytosolic calcium （[Ca^2＋]cyt） oscillations in guard cells and various oscillations in stomatal apertures. Exactly how [Ca^2＋]cyt oscillation signaling functions in stomatal oscillation is not known. In the present study, the epidermis of broad bean （Vicia faba L.） was used and a rapid ion-exchange treatment with two shifting buffers differing in K^＋ and Ca^2＋ concentrations was applied. The treatment for fivetransients at a 10-min transient period induced clear and regular stomatal oscillation. However, for other transient numbers and periods, the treatments induced some Irregular oscillations or even no obvious oscillations in stomatal aperture. The results indicate that stomatal oscillation Is encoded by parameter-specific [Ca^2＋]cyt oscillation： the parameters of [Ca^2＋]cyt oscillation affected the occurrence rate and the parameters of stomatal oscillation. The water channel inhibitor HgCl2 completely Inhibited stomatal oscillation and the inhibitory effect could be partially reversed by β-mercaptoethanol （an agent capable of reversing water channel inhibition by HgCl2）. Other Inhibitory treatments against Ion transport （i.e. the application of LaCIs, EGTA, or tetraethylammonlum chloride （TEACI）） weakly impaired stomatal oscillation when the compounds were added after rapid ion-exchange treatment. If these compounds were added before rapid-ion exchange treatment, the inhibitory effect was much more apparent （except In the case of TEACI）. The results of the present study suggest that water channels are involved In stomatal oscillation as a downstream element of [Ca^2＋]cyt oscillation signaling.

Blossom-end rot:a century-old problem in tomato(Solanum lycopersicum L.)and other vegetables

Blossom-end rot(BER)is a devastating physiological disorder affecting vegetable production worldwide.Extensive research into the physiological aspects of the disorder has demonstrated that the underlying causes of BER are associated with perturbed calcium(Ca^(2+))homeostasis and irregular watering conditions in predominantly cultivated accessions.Further,Reactive Oxygen Species(ROS)are critical players in BER development which,combined with unbalanced Ca^(2+)concentrations,greatly affect the severity of the disorder.The availability of a high-quality reference tomato genome as well as the whole genome resequencing of many accessions has recently permitted the genetic dissection of BER in segregating populations derived from crosses between cultivated tomato accessions.This has led to the identification of five loci contributing to BER from several studies.The eventual cloning of the genes contributing to BER would result in a deeper understanding of the molecular bases of the disorder.This will undoubtedly create crop improvement strategies for tomato as well as many other vegetables that suffer from BER.