Expression of Inositol 1,4,5-trisphosphate Receptor mRNA in Myocardium of Spontaneous Hypertension Rats and Cultured Vascular Smooth Muscle Cells of Rats

Objective\ To investigate expression of inositol 1,4,5 trisphosphate receptor (IP\-3R) mRNA on sacroplasmic reticular in myocardium of spontaneous hypertension rats (SHRs) and cultured vascular smooth muscle cells (VSMC) of rats and effects of perindopril and urapidil on them. Methods\ SHRs were orally given perindopril (1.0 mg·kg\+\{ 1\}·d\+\{ 1\}) or urapidil (15 mg·kg\+\{ 1\}·d\+\{ 1\}) for 24 weeks, respectively. Expression of IP\-3R mRNA was examined by semi quantitative reverse transcription polymers chain reaction (RT PCR) using three oligonuclotide primers for each subtype of IP\-3R with β actin as internal label. Results\ All subtypes of IP\-3R were expressed in myocardium of SHR, WKY and cultured VSMC. Expression of IP\-3R mRNA in left ventricle of SHR was markedly enhanced. Urapidil could down regulate expression of IP\-3R Ⅰand IP\-3R Ⅲ, perindopril slightly increased expression of IP\-3R Ⅱ and decreased expression of IP\-3R Ⅰand IP\-3R Ⅲ in myocardium of SHR. Conclusion\ Our results suggest that expression of IP\-3R mRNA in cardiovascular system could be regulated by urapidil and perindopril.

Inositol 1,4,5-trisphosphate receptor in the liver:Expression and function

The liver is a complex organ that performs several functions to maintain homeostasis.These functions are modulated by calcium,a second messenger that regulates several intracellular events.In hepatocytes and cholangiocytes,which are the epithelial cell types in the liver,inositol 1,4,5-trisphosphate(InsP3)receptors(ITPR)are the only intracellular calcium release channels.Three isoforms of the ITPR have been described,named type 1,type 2 and type 3.These ITPR isoforms are differentially expressed in liver cells where they regulate distinct physiological functions.Changes in the expression level of these receptors correlate with several liver diseases and hepatic dysfunctions.In this review,we highlight how the expression level,modulation,and localization of ITPR isoforms in hepatocytes and cholangiocytes play a role in hepatic homeostasis and liver pathology.

High expression of type I inositol 1,4,5-trisphosphate receptor in the kidney of rats with hepatorenal syndrome

AIM To detect the expression of typeⅠ inositol 1,4,5-trisphosphate receptor(IP3 RI) in the kidney of rats with hepatorenal syndrome(HRS).METHODS One hundred and twenty-five Sprague-Dawley rats were randomly divided into four groups to receive an intravenous injection of D-galactosamine(D-Gal N) plus lipopolysaccharide(LPS; group G/L, n = 50), D-Gal N alone(group G, n = 25), LPS alone(group L, n = 25), and normal saline(group NS, n = 25), respectively.At 3, 6, 9, 12, and 24 h after injection, blood, liver, and kidney samples were collected. Hematoxylineosin staining of liver tissue was performed to assess hepatocyte necrosis. Electron microscopy was used to observe ultrastructural changes in the kidney. Western blot analysis and real-time PCR were performed to detect the expression of IP3 RI protein and m RNA in the kidney, respectively.RESULTS Hepatocyte necrosis was aggravated gradually, which was most significant at 12 h after treatment with D-galactosamine/lipopolysaccharide, and was characterized by massive hepatocyte necrosis. At the same time, serum levels of biochemical indicators including liver and kidney function indexes were all significantly changed. The structure of the renal glomerulus and tubules was normal at all time points. Western blot analysis indicated that IP3 RI protein expression began to rise at 3 h(P < 0.05) and peaked at 12 h(P < 0.01). Real-time PCR demonstrated that IP3 RI m RNA expression began to rise at 3 h(P < 0.05) and peaked at 9 h(P < 0.01).CONCLUSION IP3 RI protein expression is increased in the kidney of HRS rats, and may be regulated at the transcriptional level.

Inositol 1,4,5-trisphosphate 3-kinases:functions and regulations

Inositol 1,4,5-trisphosphate 3-kinase (IP3 3-kinase/IP3K) plays an important role in signal transduction in animal cellsby phosphorylating inositol 1,4,5-trisphosphate (IP3) to inositol 1,3,4,5-tetrakisphosphate (IP4). Both IP3 and IP4 arecritical second messengers which regulate calcium (Ca2+) homeostasis. Mammalian IP3Ks are involved in many biologicalprocesses, including brain development, memory, learning and so on. It is widely reported that Ca2+ is a canonicalsecond messenger in higher plants. Therefore, plant IP3K should also play a crucial role in plant development. Recently,we reported the identification of plant IP3K gene (AtIpk2β/AtIP3K) from Arabidopsis thaliana and its characterization.Here, we summarize the molecular cloning, biochemical properties and biological functions of IP3Ks from animal, yeastand plant. This review also discusses potential functions of IP3Ks in signaling crosstalk, inositol phosphate metabolism,gene transcriptional control and so on.

1,4,5-三磷酸肌醇受体及其在休克中的作用

1,4,5-三磷酸肌醇(IP3)受体(IP3R)是内质网释放钙离子(Ca2+)的主要通道之一,在维持细胞内钙稳态方面发挥着重要作用。休克作为一种严重的、发生器官功能障碍与结构损伤的病理过程,钙稳态失调是其重要的中间环节。鉴于IP3R功能或表达异常引起钙稳态失调参与了多种病理过程的发生、进展,本文对IP3R结构与调节的研究进展进行综述,总结IP3R在失血性休克、感染性休克中的作用,期望以IP3R为切入点,为防治重症休克提供理论基础,并探索靶向IP3R防治休克的新策略。

Altered expression of stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs)in cancer:will they become a new battlefield for oncotherapy?

The stromal interaction molecule(STIM)-calcium release-activated calcium channel protein(ORAI) and inositol1,4,5-trisphosphate receptors(IP_3Rs) play pivotal roles in the modulation of Ca^(2+)-regulated pathways from gene transcription to cell apoptosis by driving calcium-dependent signaling processes.Increasing evidence has implicated the dysregulation of STIM-ORAI and IP_3Rs in tumorigenesis and tumor progression.By controlling the activities,structure,and/or expression levels of these Ca^(2+)-transporting proteins,malignant cancer cells can hijack them to drive essential biological functions for tumor development.However,the molecular mechanisms underlying the participation of STIM-ORAI and IP_3Rs in the biological behavior of cancer remain elusive.In this review,we summarize recent advances regarding STIM-ORAI and IP_3Rs and discuss how they promote cell proliferation,apoptosis evasion,and cell migration through temporal and spatial rearrangements in certain types of malignant cells.An understanding of the essential roles of STIM-ORAI and IP_3Rs may provide new pharmacologic targets that achieve a better therapeutic effect by inhibiting their actions in key intracellular signaling pathways.

1,4,5-三磷酸肌醇受体与神经变性疾病

1,4,5-三磷酸肌醇受体(inositol 1,4,5-trisphosphate receptors,IP3Rs)是细胞内质网上的钙离子(cal⁃cium ion,Ca^(2+))通道,通过调控Ca^(2+)参与细胞生物学功能,是维持中枢神经系统正常功能的关键分子。近年来,越来越多的研究发现,IP3Rs结构和功能异常与神经变性疾病如阿尔茨海默病、帕金森病、亨廷顿病、脊髓小脑共济失调等的发病机制密切相关,这些结构和功能异常如何影响IP3Rs功能,及相关钙信号,并且如何在这些疾病的发病和严重程度中发挥作用,仍尚不清楚。IP3Rs如何在神经变性疾病中发挥作用将于本文中进行综述。

Temperature-dependence and conformational basis of inositol 1,4,5-trisphosphate receptor regulated by Ca^(2+)

The inositol 1,4,5-trisphosphate (lnsP3) receptor was purified from bovine cerebellum and reconstituted in liposomes composed of phosphatidylcholine (PC) and phosphatidylethanola-mine (PE) (1:1) successfully. No effect of Ca2+ concentration on [3H]-lnsP3 binding to unreconsti-tuted lnsP3 receptor could be observed either at 4℃ or at 25℃, whereas the effect of [Ca2+] on reconstituted lnsP3 receptor depended on the temperature. The Ca2+ concentration outside the proteolipsome ([Ca2+]o) had no detectable effect on lnsP3 binding to lnsP3 receptor at 4℃. In contrast, with increase of [Ca2+]o from 0 to 100 nmol/L at 25℃, the lnsP3 binding activity increased gradually. Then the lnsP3 binding activity was decreased drastically at higher [Ca2+]0 and inhibited entirely at 50 nmol/L [Ca2+]. Conformational studies on intrinsic fluorescence of the reconstituted lnsP3 receptor and its quenching by Kl and HB indicated that the global conformation of reconstituted lnsP3 receptor could not be affected by [Ca2+]o

内质网蛋白44(ERp44)通过1,4,5-三磷酸肌醇受体介导基因转录(英文)

细胞核内钙离子浓度的增加可以引起包括钙离子激活的基因转录在内的很多生理功能.运用Western blot、免疫荧光、实时定量聚合酶链反应、钙成像以及外源三磷酸腺苷刺激细胞释放钙离子等试验方法,发现1,4,5-三磷酸肌醇受体和内质网蛋白44(ERp44)在内质网和核膜上都有很好的共定位.外源三磷酸腺苷可以通过1,4,5-三磷酸肌醇受体刺激核内钙瞬变并磷酸化环磷酸腺苷反应原件结合蛋白(CREB)、刺激原癌基因c-Myc的表达.但是,这些功能都能被1,4,5-三磷酸肌醇受体抑制剂2-氨乙氧基二苯酯硼酸(2-APB)和过表达内质网蛋白44(ERp44)所抑制.这些结果均提示在子宫颈癌HeLa细胞中内质网蛋白44(ERp44)通过1,4,5-三磷酸肌醇受体而介导基因转录.

大鼠心肌缺血再灌注时心肌细胞核1,4,5三磷酸肌醇受体结合特性改变的研究

目的观察大鼠心肌缺血再灌注时心肌细胞核1,4,5三磷酸肌醇受体(IP3R)的结合特性改变,进一步探索心肌缺血再灌注时细胞凋亡的病理机制。方法TUNEL技术检测心肌细胞核凋亡率。蔗糖密度梯度离心法提纯心肌细胞核,放射配体分析法检测心肌细胞核膜上IP3R的结合特性变化。结果①缺血再灌注损伤(IRI)组大鼠心肌细胞凋亡率高于对照组(P<0.01)。②大鼠心肌缺血再灌注损伤时,心肌细胞核IP3R的最大结合容量Bmax较假手术组增加2.6倍;而其亲和力Kd值无明显变化。③IRI组心肌细胞核IP3R经激活的PKC磷酸化后结合特性增强1.54倍,对照组核IP3R经PKC磷酸化后结合特性无明显改变。④[Ca2+]对IRI组及假手术组心肌细胞核IP3R的调节均呈双相性,胞浆钙超载状态下([Ca2+]为5μmol·L-1时)较正常胞浆钙浓度下([Ca2+]为100nmol·L-1时),两组核IP3R结合特性均增强,[Ca2+]为100μmol·L-1时,两组核IP3R结合特性降低。结论大鼠心肌心肌缺血再灌注损伤病理情况下心肌细胞核IP3R结合特性增强,致核内钙浓度([Ca2+]n)增高,这可能是心肌缺血再灌注损伤中心肌细胞凋亡的主要病理机制之一。

肿瘤坏死因子-α增强肝肾综合征时肾脏I型1,4,5-三磷酸肌醇受体表达

目的:通过观察TNF-α对肾组织中Ⅰ型IP3R表达的影响来探讨肝肾综合征的发病机制.方法:制备大鼠离体肾灌注模型,随机分成对照组(A组)、肝素处理组(B组)、TNF-α处理组(C组),留取的标本应用免疫组织化学技术、Westernblot及实时定量PCR检测肾组织Ⅰ型IP3R蛋白的定位、表达及mRNA的变化.结果:Ⅰ型IP3R主要分布于肾小球系膜细胞和血管平滑肌细胞的胞质内.免疫组化结果显示,C组与A组相比棕褐色颗粒着色的阳性细胞明显增多,有显著性差异(U=2.26,P<0.05);B组与A组相比阳性染色细胞无明显减少(P>0.05);Western blot结果与免疫组织化学结果相一致:C组与A组相比Ⅰ型IP3R蛋白表达水平明显增高,有显著性差异(1.89±0.11vs0.55±0.03,P<0.05);B组与A组相比无显著性差异(P>0.05);实时定量PCR结果显示:C组与A组相比Ⅰ型IP3R mRNA的表达水平明显增高,有显著性差异(7.99±0.12vs1.00±0.05,P<0.05);B组与A组相比无显著性差异(P>0.05).结论:TNF-α可增强肾小球系膜细胞和血管平滑肌细胞Ⅰ型IP3R蛋白的表达,且Ⅰ型IP3R mRNA也呈增加趋势.

TNF-α增强主动脉平滑肌细胞内1型1,4,5-三磷酸肌醇受体表达参与感染性休克的发生机制

目的研究TNF-α对主动脉平滑肌细胞(VSMC)内1型1,4,5-三磷酸肌醇受体(IP3RⅠ)表达的影响,揭示TNF-α影响VSMC收缩功能参与感染性休克的发生机制。方法原代分离培养大鼠VSMC。按TNF-α处理的不同时间点(0、4、8、24h)分4组。分别应用Western blot、免疫荧光、RT-PCR、双荧光素酶检测方法,观察TNF-α对IP3RⅠmRNA、蛋白表达及其启动子活性的影响。结果 TNF-α处理组细胞内IP3RⅠ分布未见变化,8、24h组荧光强度增强提示IP3RⅠ蛋白含量增加,IP3RⅠ蛋白表达升高(4h:1.059±0.005 vs 1.000±0.002,P=0.010;8h:2.416±0.042 vs 1.000±0.002,P<0.01;24h:2.138±0.010vs 1.000±0.002,P<0.01,n=9),IP3RⅠmRNA表达明显增加(4h:2.260±0.889 vs 1.00±0.02,P=0.193;8h:5.449±2.279 vs1.00±0.02,P=0.000;24h:3.049±1.684 vs 1.00±0.02,P=0.042,n=9)。转染PGL3-IP3RⅠpromoter质粒后TNF-α组IP3RⅠ启动子活性明显增强(3.56±0.65 vs 1.00±0.05,P=0.020,n=9)。结论 TNF-α可上调IP3RⅠ基因启动子活性,从而引起IP3RⅠ蛋白表达升高,增强VSMC内IP3Rs系统介导的Ca2+释放作用,这可能是TNF-α影响VSMC收缩功能参与感染性休克血管调控的机制之一。

1,4,5-三磷酸肌醇受体与心血管疾病

1,4,5-三磷酸肌醇受体是一种细胞内Ca2+释放通道,它与1,4,5-三磷酸肌醇结合后,引起Ca2+浓度发生改变,从而参与钙信号转导,调节多种细胞代谢活动。近年来,越来越多的研究提示其参与心力衰竭、心肌肥厚、心房颤动等心血管疾病的发生。现就三磷酸肌醇受体的结构、分布、激活Ca2+通道开放以及与心血管疾病发病机制的研究进展等作一综述。

1,4,5-三磷酸肌醇受体3促进常染色体显性遗传性多囊肾病囊泡生长

本文旨在阐明1,4,5-三磷酸肌醇受体3(inositol 1,4,5-trisphosphate receptor 3,IP_(3)R3)在常染色体显性遗传性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)肾囊泡发生、发展过程中的作用,为ADPKD的治疗提供理论基础。使用2-氨基乙氧基二苯基硼酸盐(2-aminoethoxy-diphenyl borate,2-APB)和shRNA抑制IP_(3)R3的表达水平,通过MDCK(MadinDarby canine kidney)囊泡模型、胚胎肾囊泡模型、肾脏特异性Pkd1敲除(PKD)小鼠模型探究IP_(3)R3在囊泡生长过程中的作用,并通过Western blot、免疫荧光染色技术探究IP_(3)R3调控囊泡生长的分子机制。结果显示,在PKD小鼠肾脏中,IP_(3)R3的表达水平显著升高。在胚胎肾囊泡模型和MDCK囊泡模型中,通过2-APB或shRNA抑制IP_(3)R3的表达可显著延缓囊泡的生长。机制研究结果显示,在ADPKD肾囊泡生长过程中,异常活化的cAMP-PKA信号通路促进了IP_(3)R3的表达,并促进其从内质网向细胞间连接处转运。IP_(3)R3的上调以及亚细胞定位的异常激活MAPK和mTOR信号通路,加速细胞周期,引起囊泡上皮细胞异常增殖,最终促进囊泡的生长。上述结果提示,IP_(3)R3在促进ADPKD肾囊泡生长过程中发挥重要作用,抑制IP_(3)R3的表达及亚细胞再分布过程可以有效延缓囊泡的生长,而IP_(3)R3有望成为ADPKD的治疗靶点。

三磷酸肌醇、钙离子在胃泌素促人结肠癌SW480细胞株增殖中的作用

目的：探讨胃泌素对人结肠癌细胞株ＳＷ４８０内三磷酸肌醇（ＩＰ３）、钙离子（Ｃａ２＋）的影响及其在细胞增殖中的作用，为结肠癌抗信息传导治疗提供实验依据。方法：①３Ｈ－肌醇标记细胞进行ＩＰ３分析。②应用Ｃａ２＋荧光指示剂Ｆｕｒａ－２检测细胞内Ｃａ２＋的浓度。③ＭＴＴ比色分析法检测活细胞数（吸光度Ａ值）。结果：５肽胃泌素（Ｐｅｎｔａｇａｓｔｒｉｎ，ＰＧ）可使ＳＷ４８０细胞内ＩＰ３、Ｃａ２＋水平升高，同时活细胞数Ａ值增加；５肽胃泌素与其受体拮抗剂丙谷胺（Ｐｒｏｇｌｕｍｉｄｅ，ＰＧＬ）合用时，癌细胞内ＩＰ３、Ｃａ２＋水平和活细胞数Ａ值均无明显变化。

暴发性肝衰竭时肾脏Ⅰ型1，4，5-三磷酸肌醇受体表达增加

目的 研究暴发性肝衰竭小鼠肾脏I型1,4,5-三磷酸肌醇受体（IP3R）表达的变化。方法 采用D-氨基半乳糖和内毒素联合腹腔注射制备暴发性肝衰竭小鼠动物模型。动物随机分为4组,即等渗盐水对照组、LPS对照组、D-氨基半乳糖对照组、暴发性肝衰竭组（2、6、9 h）。应用免疫组织化学、Western blot及RT-PCR技术检测暴发性肝衰竭进程中,小鼠肾脏IP3R蛋白质的定位、表达及mRNA表达的变化。结果 Ⅰ型IP3R主要分布于肾小球系膜细胞和血管平滑肌细胞的胞浆内。在暴发性肝衰竭组小鼠,6 h时I型IP3R免疫组织化学染色阳性细胞开始增加,9 h时更为明显（6 h：x^2=7．11,P〈0．01,9 h： x^2=9．15,P〈0.01）。Western blot结果与免疫组织化学结果一致,6 h时开始增加（t=3．16,P〈0．05）,9 h达到最高值（t=5．43,P〈0．01）,与等渗盐水对照组相比差异有统计学意义。RT PCR结果显示暴发性肝衰竭小鼠2 h时I型IP3R mRNA即开始增加,6 h时达到最高值,9 h时有所恢复,但与等渗盐水对照组相比差异均有统计学意义（2 h：t=2．47,P〈0．05,6 h：t=4．42,P〈0.01,9 h：t=2．16,P〈0．05）。结论 在暴发性肝衰竭进程中,肾脏I型1,4,5-三磷酸肌醇受体表达增强,其mRNA也呈上调趋势。

肝硬化大鼠肾小球血管袢和肾小球前小动脉Ⅰ型1,4,5-三磷酸肌醇受体的表达

目的 探讨跨膜信息传导机制在肝硬化并肝肾综合征发病机制中的作用。 方法 应用40％四氯化碳制备肝硬化动物模型,免疫组织化学方法检测肝硬化大鼠肾小球血管袢和肾小球前小动脉的Ⅰ型1,4,5-三磷酸肌醇受体(IP3R),观察其表达情况。 结果 肾小球血管袢和肾小球前小动脉Ⅰ型IP3R表达,实验组分别为:4.97±1.34、4.09±1.14,正常大鼠组分别为:2.43±1.67、1.83±1.32,两组之间差异有非常显著性,t值分别为3.43和3.70,P值分别为0.0037和0.0022;实验组肾小球血管袢和肾小球前小动脉Ⅰ型IP3R表达,差异有显著性,t值为2.28,P=0.0458。大鼠肾脏常规病理检查均无改变。 结论 跨膜信息传导机制在肝硬化并肝肾综合征发生机制中发挥重要作用。

蛋白激酶C调节的1,4,5-三磷酸肌醇受体磷酸化在胆囊收缩素介导的胃窦平滑肌细胞钙动员中的作用

目的研究八肽胆囊收缩素(CCK-8)对大鼠胃窦平滑肌细胞(SMC)胞内钙释放和胞外钙内流的作用及对其具体相关机制的探讨。方法 (1)多导生理记录仪记录大鼠离体胃窦肌条在不同条件下的收缩活动;(2)免疫印迹法和免疫沉淀法检测胃窦 SMC 的三型1,4,5-三磷酸肌醇受体(Ins P_3R3)及其磷酸化水平;(3)Fura-2/AM 标记胃窦 SMC,观察 CCK-8S 对胞内钙离子浓度([Ca^(2+)]i)的影响;(4) 全细胞膜片钳检测胃窦 SMC 的 L-型电压门控钙通道电流(I_(Ca-L))的变化情况。结果(1)CCK-8S作用下胃窦肌条收缩幅值和频率改变明显[增长率分别为(62±13)%和(58±17)%,均P<0.01],可被 CCK-A 受体拮抗剂和钙泵抑制剂所阻断;(2)蛋白激酶 C(PKC)上调 InsP_3 R3磷酸化水平,抑制 CCK-8S 介导的内钙释放;(3)CCK-8S 引起的[Ca^(2+)]i 显著升高[从(69±7)mol/L 升至(472±36)nmol/L,P<0.01]分别可被 CCK-A 受体或胞内钙泵抑制剂和 PKC 激动剂所阻断;去除外钙或给予 L-型钙通道阻滞剂时 CCK-8S 仍可引起[Ca^(2+)]i 升高;(4)CCK-8S 显著增强胃窦 SMC 的I_(Ca-L)[从(-56±7)pA 升至(-89±6)pA,P<0.01],可分别被 I_(Ca-L)阻滞剂、胞内钙泵抑制剂和钙依赖性氯通道阻滞剂所阻断。结论 CCK-8S 引起的大鼠胃窦 SMC 的[Ca^(2+)]i 升高依赖于 PKC 介导的InsP_3R3磷酸化作用调节下的细胞内钙离子释放。胞内钙释放可激活 I_(Cl-Ca),引起细胞膜去极化而活化 I_(Ca-L)引起胞外钙内流,最终引起 SMC 收缩效应。

1,4,5-三磷酸肌醇3激酶A调控脑胶质瘤细胞增殖、迁移和上皮间质化

目的探讨1,4,5-三磷酸肌醇3激酶A(ITPKA)在脑胶质瘤细胞的表达和功能。方法利用实时定量聚合酶链反应(PCR)和蛋白质印迹法(Western blot)比较SVGP12、U118和U87细胞系(购自中国科学院生物化学与细胞生物学研究所)ITPKA mRNA和蛋白表达水平。将U87细胞分为对照组、对照短发卡RNA(shRNA)组和sh-ITPKA组,噻唑蓝法检测转染细胞培养24、48、72、96 h后细胞活性,平板克隆和小室迁移(Transwell)法检测克隆形成能力与细胞迁移能力,Western blot检测ITPKA、波形蛋白、N-钙黏蛋白和E-钙黏蛋白表达水平。多组间比较采用单因素方差分析或双因素方差分析。结果U118和U87细胞中ITPKA mRNA和蛋白表达水平明显高于SVGP12细胞(mRNA水平:2.81±0.40、3.92±0.19比1.06±0.06,F=94.48,P<0.01;蛋白水平:0.57±0.05、0.66±0.03比0.20±0.01,F=161.30,P<0.01)。培养24、48、72、96 h后,sh-ITPKA组细胞活性明显低于对照组和对照shRNA组(24 h:0.14±0.01比0.19±0.01、0.20±0.02,P<0.01;48 h:0.20±0.01比0.30±0.01、0.30±0.02,P<0.01;72 h:0.26±0.01比0.37±0.01、0.38±0.01,P<0.01;96 h:0.29±0.01比0.45±0.01、0.45±0.01,F_(交互)=17.22,F_(时间)=713.00,F_(分组)=662.60,P<0.01)。sh-ITPKA组细胞细胞迁移数目低于对照组和对照shRNA组(25.40±2.51比41.20±4.66、42.00±5.24,F=23.69,P<0.01)。同时,sh-ITPKA组细胞克隆形成数目明显低于对照组和对照shRNA组(120.60±11.41比215.00±18.73、221.40±14.83,F=68.15,P<0.01)。sh-ITPKA组细胞ITPKA、波形蛋白、N-钙粘蛋白表达水平低于对照组和对照shRNA组,而E-钙粘蛋白表达则高于对照组和对照shRNA组(ITPKA:0.11±0.02比0.70±0.02、0.68±0.03,F=637.00,P<0.01;波形蛋白:1.06±0.07比1.65±0.07、1.60±0.08,F=58.31,P<0.01;N-钙粘蛋白:0.88±0.04比1.15±0.07、1.20±0.03,F=31.56,P<0.01;E-钙粘蛋白:0.85±0.03比0.46±0.04、0.43±0.04,F=116.80,P<0.01)。结论ITPKA在胶质瘤细胞中表达升高,敲低ITPKA表达则抑制胶质瘤细胞恶性行为。

肌醇1,4,5-三磷酸受体与阿尔茨海默病

细胞内质网上的肌醇1,4,5-三磷酸受体(inositol 1,4,5-trisphosphate receptors, IP3Rs)是调节Ca^2+释放的重要离子通道。Ca^2+稳态是维持机体细胞生理功能的重要基础,Ca^2+信号参与酶激活、囊泡释放和细胞凋亡等多种细胞过程。研究表明,Ca^2+信号异常与阿尔茨海默病(Alzheimer’s disease, AD)密切相关,神经元中钙信号异常可以导致细胞稳态失衡、突触功能丧失,甚至细胞死亡。现对IP3Rs的生物特性及其介导的Ca2+释放在阿尔茨海默病发生发展过程中的作用进行综述。