Roles of Na^+/Ca^(2+) exchanger 1 in digestive system physiology and pathophysiology

The Na^+/Ca^(2+) exchanger(NCX) protein family is a part of the cation/Ca^(2+) exchanger superfamily and participates in the regulation of cellular Ca^(2+) homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption.This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.

Life after the birth of the mitochondrial Na^+/Ca^(2+) exchanger,NCLX

Powered by the mitochondrial membrane potential,Ca2+ permeates the mitochondria via a Ca2+ channel termed Ca2+ uniporter and is pumped out by a Na+/Ca2+ exchanger,both of which are located on the inner mitochondrial membrane.Mitochondrial Ca2+ transients are critical for metabolic activity and regulating global Ca2+ responses.On the other hand,failure to control mitochondrial Ca2+ is a hallmark of ischemic and neurodegenerative diseases.Despite their importance,identifying the uniporter and exchanger remains elusive and their inhibitors are non-specific.This review will focus on the mitochondrial exchanger,initially describing how it was molecularly identified and linked to a novel member of the Na+/Ca2+ exchanger superfamily termed NCLX.Molecular control of NCLX expression provides a selective tool to determine its physiological role in a variety of cell types.In lymphocytes,NCLX is essential for refilling the endoplasmic reticulum Ca2+ stores required for antigen-dependent signaling.Communication of NCLX with the store-operated channel in astroglia controls Ca2+ influx and thereby neuro-transmitter release and cell proliferation.The refilling of the Ca2+ stores in the sarcoplasmic reticulum,which is controlled by NCLX,determines the frequency of action potential and Ca2+ transients in cardiomyocytes.NCLX is emerging as a hub for integrating glucose-dependent Na+ and Ca2+ signaling in pancreatic β cells,and the specific molecular control of NCLX expression resolved the controversy regarding its role in neurons and β cells.Future studies on an NCLX knockdown mouse model and identification of human NCLX mutations are expected to determine the role of mitochondrial Ca2+ efflux in organ activity and whether NCLX inactivation is linked to ischemic and/or neurodegenerative syndromes.Structure-function analysis and protein analysis will identify the NCLX mode of regulation and its partners in the inner membrane of the mitochondria.

Na^＋/Ca^2＋ Exchanger 3 is Downregulated in the Hippocampus and Cerebrocortex of Rats with Hyperthermia-induced Convulsion

Background： Na^＋/Ca^2＋ exchanger （NCX） plays a crucial role in pentylenetetrazol-induced convulsion. However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion. In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion. Methods： Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group （n = 7 in each group）. Whole-cell patch-clamp method was used to record NCX currents. Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3. Results： NCX currents were decreased in rats after febrile convulsion. Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively. Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures. Conclusions： There is a significant reduction in NCX3 expression in rats with febrile convulsions. Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.

Downregulation of Na^＋/Ca^2＋ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

Background：Calcium regulatory proteins-L-type Ca^2＋ channels （LTCCs）,ryanodine receptor 2 （RyR2）,and Na^＋/Ca^2＋ exchanger isoform 1 （NCX1） have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury （I/RI）.Both sevofturane postconditioning （SevoPoC） and delayed remote ischemic preconditioning （DRIPC） have been shown to protect the heart against I/RI.In this study,we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model.Methods：After 30-min balanced perfusion,isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion.Totally 40 isolated hearts were randomly assigned to four groups （n =10/group）：time control group,I/RI group,SevoPoC group,and DRIPC group.The effect of SevoPoC （3% v/v） and DRIPC were observed.Myocardial infarct size （IS）,cardiac troponin I level,and heart function were measured.The protein and messenger RNA levels of LTCCs,RyR2,and NCX1 were determined.Results：Both SevoPoC and DRIPC improved the recovery of myocardial function,and reduced cardiac troponin Ⅰ release after I/RI.The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group （16.50% ± 4.54% in the SevoPoC group [P =0.0006],and 22.34% ± 4.02% in the DRIPC group [P =0.0007] vs.35.00% ± 5.24% in the I/RI group,respectively）.SevoPoC,but not DRIPC significantly inhibited the activity of NCX 1 （0.59 ＋ 0.09 in the I/RI group vs.0.32 ± 0.16 in the SevoPoC group,P =0.006;vs.0.57 ± 0.14 in the DRIPC group,P =0.072）.No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC.In addition,subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin Ⅰ level and the protein expression ofNCX1 （r =0.505,P =0.023）.Conclusion：SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.

陕西某矿区煤泥制备4A分子筛的试验研究

以陕西某矿区煤泥为原料,采用水热方法合成4A型分子筛。通过单因素试验,分别研究了nNa_(2)O/nSiO_(2)比、老化时间、晶化温度和晶化时间对4A分子筛的Ca^(2+)交换量的影响。优化后的合成条件为:nNa_(2)O/nSiO_(2)=1.3,老化时间是8h,晶化温度是85℃,晶化时间是6h。通过XRD和SEM分析检测表明,晶体呈现规则的立方体形状,颗粒大小均匀,晶体粒径在1μm左右,实验制得的4A分子筛的Ca2+交换量达到293.53mg·g^(-1),静态水吸附量达到22.3%。

以煤泥为原料的4A分子筛的水热合成

以黄陵煤泥为原料,利用水热法合成4A型分子筛。采用XRD、FT-IR和SEM对4A分子筛样品进行表征,并对样品进行性能测试,结果表明:样品4A分子筛的结晶度高,无其他晶体生成,骨架结构完整,颗粒大小均匀,粒径约为2μm。合成的4A分子筛产品钙离子交换量297.6g/mg,静态水吸附量21.5%,灼烧失量19.7%,p H值10,均达到洗涤剂用4A分子筛行业标准。

几种代磷助剂的性能比较

分析了几种代磷助剂的主要成分与结构组成,测试了其溶解性、pH值、Ca2+交换能力与抗酸能力,比较了助剂在无磷粉中对粉体成型、白度、去污及循环洗涤等性能的影响作用。结果表明,几种代磷助剂的综合性能介于4A沸石与三聚磷酸钠(STPP)间,1#助剂的性价比较优,但颜色较深;6#、7#助剂的钙交换力与抗酸能力强,但价格却偏高;助剂的pH值总体偏高。

Effect specificity of the early intervention with moxibustion at“BL23”in Alzheimer’s disease rats modeled by ovariectomy and D-Galactose injection

Objective:To observe the effect of the early intervention with moxibustion at "Shènshū(肾俞BL23)" on learning and memory of Alzheimer’s disease(AD) rats modeled by ovariectomy and D-Galactose(D-Gal)injection and the effect on Ca2+/CaMKII/CREB signaling pathway so as to provide the evidence for the acupoint selection in the early intervention with acupuncture and moxibustion for AD.Methods:Sixty female SD rats at the age of 3 months were selected and randomly divided into a normal group,a sham-operation group,a model group,a "BL23" group,a "Wèishū"(胃俞BL21) group,and a non-acupoint group,10 rats in each group.Except in the normal group and the sham-operation group,bilateral ovaries were removed in the other 4 groups.3 days after the operation,D-Gal was injected intraperitoneally at a dose of 150 mg/kg/d for 90 days to establish AD rat model.In the sham-operation group,only the peripheral fat of ovarian was removed and 0.9% normal saline was injected intraperitoneally of the same dose for 90 days.In the "BL23" group,the "BL21" group and the non-acupoints group,since the 2 nd day after ovariectomy,moxibustion was applied at 9:00 a.m.every day in the rats.The rats were fixed on a fixed table,the mild moxibustion with self-prepared moxa stick was applied to bilateral "BL23""BL21" and the non-acupoint of each rat,the ignited end of moxa stick was 2 cm to 3 cm far from skin surface.The infrared thermometer was adopted to measure the temperature of the epidermis of each acupoint from time to time so as to maintain the local temperature to be(41 ± 0.5)℃.Mild moxibustion lasted for 10 min each time,consecutively for 5 days a week and at an interval of 2 days.The total consecutive intervention duration was 12 weeks.In the normal group and the shamoperation group,no moxibustion intervention was performed,but the rats were restricted in a same way during the experiment.At the end of modeling and intervention,water maze test was adopted to detect the learning and memory abilities of rats in each group.The western blotting was used to detect the expressions of p-CREB,p-CaMKII,CaMKII and CREB in hippocampus of rats in each group.Results:(1)Navigation test:since Day 72,compared with the sham-operation group,the escape latencies in all of the consecutive 5 days were longer in the model group(all P <0.05).Since Day 73,compared with the normal group,the escape latency in all of the consecutive 4 days was shorter in the "BL23"group(all P <0.05).(2) Times across platform:compared with the normal group,the number of times consecutively crossing the platform was lower in the model group(P <0.05).After moxibustion,compared with the model group,the number of times across platform was higher in the "BL23"group,indicating a statistical significance(P <0.05).(3)Moving track of water maze spatial probe:the "tendency"strategy was displayed in the normal group and the sham operation group.The "marginal" strategy,which is commonly seen in the AD rats,was displayed in the model group.The "random" strategy was displayed in the "BL23" group.The "marginal" strategy was presented in the "BL21" group and the non-acupoint group.(4) Expressions of hippocampal P-CAMKII,CAMKII,CREB and P-CREB in the rats:compared with the normal group,the phosphorylation degrees of CAMKII and CREB were significantly reduced(both P<0.05) in the model group.In 12 weeks of moxibustion,compared with the model group,the levels of P-CAMKII and P-CREB were increased in the "BL23" group and the "BL21" group(all P <0.05) and the levels in the "BL23" group were higher than that of the "BL21" group and the non-acupoint group(all P<0.05).Conclusion:Moxibustion at "BL23" achieves a better effect in improving the learning and memory of AD rats modeled by ovariectomy and D-Gal injection as compared with moxibustion at "BL21" and the non-acupoint.The effect mechanism is potentially related to the effective activation of Ca2+/CaMKII/CREB signaling pathway.