Neuroligin对SH-SY5Y细胞增殖和凋亡的影响

目的:探讨Neuroligin(NLG)对人神经母细胞瘤SH-SY5Y增殖和凋亡的影响。方法:体外培养SH-SY5Y细胞24 h后,分别用浓度为50,100,200μmol/L的NLG siRNA转染SH-SY5Y细胞并共孵育24 h,然后采用噻唑蓝(MTT)法检测不同浓度NLG siRNA对SHSY5Y细胞增殖率的影响,以及Real-time PCR法检测SH-SY5Y细胞中凋亡基因Bax、Bcl-2、Bcl-x L和caspase-9基因表达水平的变化。结果:与空白对照组及siRNA阴性对照组相比,转染NLG siRNA后SH-SY5Y细胞增殖率显著下降,细胞凋亡相关基因被激活,导致细胞凋亡。结论:NLG对神经元细胞具有保护作用,抑制神经细胞凋亡。     

低氧诱导因子-1α对SH-SY5Y细胞兴奋性毒性损伤的调节作用

探讨低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)在喹啉酸诱导人神经母细胞瘤SH-SY5Y细胞损伤中的作用。将体外培养的人神经母细胞瘤SH-SY5Y细胞分为对照组、喹啉酸低、中、高剂量组及HIF-1α抑制剂二甲氧基雌二醇(2-methoxyestradiol,2ME2)预处理喹啉酸高剂量组,采用噻唑蓝还原法和乳酸脱氢酶漏出率检测法测定细胞损伤程度,Hoechst 33342单荧光染色法观察细胞凋亡,免疫荧光染色法检测HIF-1α在细胞内的表达,免疫印迹法检测细胞HIF-1α、蛋白激酶B(protein kinase B,Akt)、磷酸化Akt(p-Akt)、Bcl-2和Bax的表达。结果显示,喹啉酸可剂量、时间依赖性地诱导SH-SY5Y细胞损伤,导致细胞凋亡。同时,喹啉酸可使SH-SY5Y细胞HIF-1α表达上调并发生核转位、p-Akt表达增加及Bax/Bcl-2表达比例增加,而2ME2可抑制喹啉酸诱导的SH-SY5Y细胞损伤及降低HIF-1α、p-Akt和Bax/Bcl-2的表达。由此说明,HIF-1α/Akt通路介导了喹啉酸诱导SHSY5Y的细胞凋亡。HIF-1α抑制剂(2ME2)能够减轻喹啉酸致SH-SY5Y细胞损伤程度,减少细胞凋亡。     

叠氮钠、过氧化氢对SH-SY5Y细胞内硫氧还蛋白还原酶的影响

过度氧化应激是诱发许多神经退变病的重要因素。叠氮钠(NaN3)是线粒体有氧呼吸链细胞色素c氧化酶(COX)的特异性抑制剂,过氧化氢(H2O2)释放氧自由基造成氧化损伤,两者都可以用于氧化应激情况下神经元损伤模型的建立。硫氧还蛋白还原酶(thioredoxin reductase,TR)特异性的还原氧化型的硫氧还蛋白(thioredoxin,TRx),调节细胞中氧化还原的平衡。现以不同浓度NaN3或H2O2,处理人神经母细胞瘤细胞(SH-SY5Y细胞),建立损伤模型。通过MTT法、形态学方法检测SH-SY5Y细胞损伤程度。同时,通过Western blot定量法、免疫细胞化学法,检测损伤的SH-SY5Y细胞中TR含量的改变,观察TR在胞内的分布。实验表明,NaN3、H2O2,均以浓度依赖方式损伤SH-SY5Y细胞;TR分布于SH-SY5Y细胞的胞浆,表明TR是一种分泌蛋白,损伤后分布无明显变化。但一定浓度的NaN3作用后3h,胞内TR水平显著降低,即神经系统内呼吸链受损可抑制TR的表达,为神经退变病的防治提供了新的思路。     

人神经母细胞瘤株中β-淀粉样前体蛋白基因IL-1反应元件的研究

细胞团子IL-1β可以诱导SH-SY5Y神经母细胞瘤细胞中APP基因的转录．为了研究APP基因启动子区的IL-1β反应元件,用含不同长度APP启动子片段的报告基因载体,瞬时转染SH-SY5Y细胞,发现APP启动子在SH-SY5Y细胞中有较强活性,其中-488到-303区为IL-1β诱导APP转录活性增加所必需,这个区域包括1个AP1结合位点和1个HSE元件．     

蜗牛多肽混合物对过氧化氢诱导的SH-SY5Y细胞PCNA表达的影响

采用H2O2诱导人神经母细胞瘤细胞株(SH-SY5Y)细胞损伤,MTT法测定细胞存活率,不同浓度蜗牛多肽混合物(SPM)处理后,Hoechst染色检测细胞凋亡,细胞免疫化学技术和Western blot技术检测细胞PCNA的表达。结果发现1.54 mmol/L H2O2可诱导SH-SY5Y细胞凋亡,PCNA的表达明显降低。经用39 mg/L(SPM-L组)和156 mg/L(SPM-H组)浓度的SPM处理后,SH-SY5Y细胞凋亡明显减少(H2O2VS.SPM-L:58.39±8.67%VS.44.06±4.35%,P0.05;H2O2VS.SPM-H:58.39±8.67%VS.32.45±9.44%,P0.01),同时PCNA的表达呈浓度依赖性升高。提示SPM可抑制H2O2诱导的SH-SY5Y细胞凋亡,其作用机制可能与其增加细胞PCNA的表达有关。     

TIMP-1基因缄默削弱SH-SY5Y细胞的增殖潜能并诱导其凋亡增强

前期研究发现,人基质金属蛋白酶组织抑制剂-1(tissue inhibitors of metalloproteinases-1,TIMP-1)在唐氏综合征（Down’s syndrome ,DS)胎儿脑组织内表达下调．为了探讨TIMP-1表达下调参与DS脑病变发生的可能机制,本研究以人神经母细胞瘤细胞（SH-SY5Y）为模型,观察TIMP-1基因沉默后对其增殖和凋亡的影响．应用LipofectaminTM2000将TIMP-1特异性短发卡 RNA( short hairpin RNA,shRNA)导入SH-SY5Y细胞,经嘌呤霉素筛选获得稳定表达TIMP-1-shRNA细胞株;应用RT-PCR、real-time PCR和Western 印迹对干扰效率进行鉴定：与SH-SY5Y细胞相比,无论在mRNA水平还是蛋白水平,SH-SY5Y-TIMP-1-shRNA细胞中TIMP-1的表达显著下调（下调率接近100%）．结果显示,已成功构建了TIMP-1基因沉默的SH-SY5Y细胞模型．在此基础上,通过MTT检测发现,TIMP-1基因沉默后SH-SY5Y细胞增殖减慢;流式细胞仪和荧光显微镜凋亡检测显示,TIMP-1基因沉默后SH-SY5Y细胞凋亡明显增加．这些研究结果表明,TIMP-1基因沉默能削弱SH-SY5Y细胞的增殖能力并增强SH-SY5Y的凋亡效应,提示TIMP-1可能是通过影响神经细胞的增殖和凋亡参与DS智力低下的发病过程．     

人钙结合蛋白S100A9基因克隆表达纯化及其对SH-SY5Y细胞作用的研究

钙结合蛋白S100A9在许多慢性疾病中聚集并可能在一些自身免疫性如老年痴呆中发挥了重要的作用。大量的报道也表明S100A9日益获得人们的注意。通过获取足量重组人S100A9蛋白,探索其对神经母细胞瘤细胞SH-SY5Y的作用及机制。运用全基因合成法合成人S100A9基因,构建人S100A9原核表达重组质粒p ET28a-S100A9,经单酶切法及PCR法鉴定重组质粒已构建成功。利用异丙基硫代-β-D-半乳糖苷(IPTG)在18℃、25℃、37℃分别诱导表达,经聚丙烯酰胺凝胶电泳(SDS-PAGE)和Western blotting鉴定,结果显示18℃时蛋白大量表达于上清中,在37℃时大量表达于包涵体。采用镍亲和层析法分别纯化两种来源重组蛋白,透析后低温冻干获得蛋白粉。使用CCK-8法检测上清来源和包涵体来源的S100A9蛋白对神经母细胞瘤细胞SH-SY5Y的增殖抑制作用。结果显示两种来源重组蛋白对SH-SY5Y细胞具有生长抑制作用,在浓度为0.05 mg/m L时即有明显抑制作用(p0.01),且二者作用无明显差异(p0.01)。采用AO/EB双重染色和流式细胞术初步检测S100A9对SH-SY5Y细胞的增殖抑制机理,结果显示该蛋白可促进SH-SY5Y细胞的凋亡。两种来源蛋白之间的比较也显示二者对于SH-SY5Y细胞作用无明显差异(p0.05)。本研究成功获得足量S100A9重组蛋白,且两种来源S100A9蛋白作用于SH-SY5Y细胞的生物学效应一致。     

阿魏酸钠生物学活性——对高糖诱导SH-SY5Y细胞凋亡的保护作用

探讨阿魏酸钠对高糖诱导的人神经母细胞瘤(SH-SY5Y)细胞凋亡的保护作用及其机制。分别通过葡萄糖培养液,以及具有阶梯阿魏酸钠含量的葡萄糖混合培养液进行SH-SY5Y细胞培养,持续时间为48 h。对其中细胞的存活率使用MTT比色法检测;通过Hoechst33258染色观察细胞核形态改变;细胞凋亡率引入流式细胞仪进行测验;离心获得细胞上清液后,使用对其中含有的8-羟基脱氧鸟苷酸(8-OHd G)组分使用酶联免疫吸附法检测。结果显示阿魏酸钠保护组细胞存活率明显升高,细胞核形态明显改善,组细胞早期凋亡率、上清液中8-OHd G的分泌量均明显降低。结果可见,阿魏酸钠对高糖诱导的SH-SY5Y细胞凋亡具有保护作用,其机制可能与阿魏酸钠的抗氧化作用有关。     

单纯疱疹病毒Ⅱ型潜伏、激活细胞模型建立

【目的】建立单纯疱疹病毒Ⅱ型(HSV-2)潜伏感染人神经母细胞瘤细胞株SH-SY5Y及激活的细胞模型。【方法】分别加入20,40,60,80,100,120,140μmol/L的阿昔洛韦(ACV),观察对SH-SY5Y细胞生物性状的影响;在ACV存在的情况下,分别将含有0.1、1、10、100MOI的病毒液接种SH-SY5Y细胞,运用相差显微镜观察病毒对细胞的影响,确定潜伏的建立;分别用41℃、42℃、43℃、44℃、45℃加热0.5h、1.0h、1.5h、2.0h、2.5h,观察加热时间及温度诱导HSV-2在SH-SY5Y细胞中激发的最适条件;加入25、50、75、100、125μmol/L福斯高林(Forskolin)诱导病毒在细胞中激活,探讨诱导的最佳浓度;对HSV-2在SH-SY5Y细胞中的潜伏及激发进行验证并测序;运用相差显微镜观察病毒激活后细胞形态的变化。【结果】60μmol/LACV的存在最适合HSV-2在SH-SY5Y细胞中建立潜伏状态;1-10MOI的感染量均能取得较好的病毒潜伏及激发效果;通过观察,病毒在SH-SY5Y细胞中最长可潜伏14d;43℃,1.5h及75μmol/LForskolin均为诱导病毒潜伏激发的最佳条件;相差显微镜观察病毒激发后细胞病变,从24h到72h,细胞变性、坏死的程度、数量随感染时间延长而增加;HSV-2LAT、gG基因PCR扩增及电泳结果,证实病毒在细胞中的潜伏及激活。【结论】初步在人神经母细胞瘤细胞株SH-SY5Y上建立了HSV-2潜伏感染及激活的细胞模型,为下一步研究HSV-2的潜伏与激发机理,了解HSV-2的致病机制打下基础。     

MAPK磷酸酯酶-1通过抑制JNK和p38的磷酸化调节SH-SY5Y神经母细胞瘤的凋亡

目的研究MKP-1在SH-SY5Y神经母细胞瘤中的抗凋亡。方法建立稳定表达MKP-1的SH-SY5Y细胞,用H2O2诱导细胞凋亡,并通过Western blotting比较分析MKP-1的表达对JNK和p38磷酸化的调节。结果①H2O2诱导SH-SY5Y细胞表达MKP-1,同时导致JNK和p38的去磷酸化;②在稳定表达MKP-1的SH-SY5Y细胞中,MKP-1可以抑制JNK和p38的磷酸化。③稳定表达MKP-1的SH-SY5Y细胞抵抗H2O2诱导细胞凋亡的能力比对照细胞提高了1倍左右。结论MKP-1对神经细胞的凋亡具有重要的调节作用,提示MKP-1作为调节ERK、JNK和p38蛋白激酶信号途径的重要分子,可能对退行性神经系统疾病的发病机制和治疗有重要的作用。     

SOD3 Ameliorates Aβ<Subscript>25–35</Subscript>-Induced Oxidative Damage in SH-SY5Y Cells by Inhibiting the Mitochondrial Pathway

This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against amyloid beta (Aβ_25–35)-induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SH-SY5Y cells overexpressing SOD3 were generated by adenoviral vector-mediated infection and Aβ_25–35 was then added to the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes and calcium images were examined. Following Aβ_25–35 exposure, SOD3 overexpression promoted the survival of SH-SY5Y cells, decreased the production of ROS, decreased MDA and calcium levels, and decreased cytochrome c, caspase-3, caspase-9 and Bax gene expression. Furthermore, SOD3 overexpression increased the expression and activity of antioxidant enzyme genes and Bcl-2 expression. Together, our data demonstrate that SOD3 ameliorates Aβ_25–35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway. These data provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage.     

Reduction of Muscarinic Receptor Density and of Guanine Nucleotide-Stimulated Phosphoinositide Hydrolysis in Human SH-SY5Y Neuroblastoma Cells Following Long-Term Treatment with 12-O-Tetradecanoylphorbol 13-Acetate or Mezerein

The actions of tumor promoters on the coupling of muscarinic receptors to the hydrolysis of inositol lipids and the generation of Ca2+ signals were examined in the human neuroblastoma SH-SY5Y cell line. Pretreatment of SH-SY5Y cells with 50 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) for 5 days resulted in neuronal differentiation, a 28% decrease in both N-[3H]methylscopolamine and [3H]-scopolamine binding, and a significantly larger reduction (48%) in agonist-stimulated 3H-inositol phosphate generation. Whereas mezerein could mimic the effects produced by TPA, the biologically inactive 4 alpha-phorbol 12,13-didecanoate was without effect on both antagonist binding and agonist-stimulated phosphoinositide (PPI) turnover. A decline (approximately 50%) in the agonist-mediated rise in cytoplasmic Ca2+ and a substantial loss of protein kinase C activity also were observed following pretreatment with TPA or mezerein. The ability of fluoride, an agent capable of direct activation of guanine nucleotide binding proteins, to stimulate 3H-inositol phosphate release was significantly reduced in SH-SY5Y cells treated with these agents. Furthermore, pretreatment of SH-SY5Y neuroblastoma cells with TPA or mezerein impaired 3H-inositol phosphate formation induced by the addition of either guanosine 5'-O-(3-thiotriphosphate) or carbamylcholine to digitonin-permeabilized cells, but not that elicited by the addition of 2 mM CaCl2. Although cells cultured in the presence of serum-free media also exhibited neuronal differentiation, no significant alteration in either muscarinic receptor number or agonist-stimulated PPI hydrolysis was observed. The results suggest that TPA and mezerein decrease agonist-stimulated PPI hydrolysis and Ca2+ signaling in SH-SY5Y cells not only by a reduction in muscarinic receptor number but also through an inhibition of guanine nucleotide-stimulated PPI turnover.     

不同能量的培养条件对人神经母细胞瘤株SH-SY5Y细胞生长的影响

目的建立热量限制的体外模型,观察不同能量培养条件下对人神经母细胞瘤细胞株SH-SY5Y细胞生长代谢的影响。方法将人神经母细胞瘤细胞株SH-SY5Y细胞分别采用含有低浓度（2 g/L）、正常浓度（3.15g/L）或高浓度（4.5 g/L）葡萄糖的培养基进行常规传代培养,利用MTT代谢率、细胞生长曲线及LDH漏出率等指标观察各组细胞生长情况。结果与正常葡萄糖浓度培养条件下培养的对照组相比,高糖组细胞突起缩短,细胞胞体皱缩,MTT代谢率稍低（0.573±0.001）,LDH漏出率高,细胞生长状态差;与对照组相比,低糖组细胞突起伸展,MTT代谢率较低（0.428±0.003）,LDH漏出率低,细胞生长速度缓慢,但是形态良好。结论高糖培养对细胞有损伤作用,细胞代谢加速,更容易衰老死亡;而低糖培养起到保护作用,在热量限制允许范围内降低培养液的含糖量,不但不会对细胞造成损伤,反而对细胞的代谢及生长起到保护作用,延长细胞的总体寿命。     

应用两种方法诱导SH-SY5Y细胞分化的研究

目的：观察全反式维甲酸（ATRA）处理和ATRA与十四烷酰佛波醇乙酸酯（TPA）序贯处理（ATRA/TPA）对人类神经母细胞瘤细胞系SH-SY5Y细胞增殖抑制和形态分化的影响。方法：应用10μM ATRA处理6天和10μM ATRA处理3天继以80 nMTPA处理3天这两种方法使SH-SY5Y细胞分化;用倒置光学显微镜动态观察SH-SY5Y细胞形态学变化;并用MTT比色法比较两种分化方法对SH-SY5Y细胞的体外抗增殖作用。结果：ATRA处理和ATRA与TPA序贯处理对SH-SY5Y细胞都有抗增值和诱导细胞分化作用,细胞形态发生明显的变化,分化成神经元表型,前者主要表现为两端带有长突起的纺锤体样细胞形态,而后者主要是由细胞体延伸出多个突起的多边形的细胞。ATRA分化6天的细胞的存活率下降为78.7%±2.0%。当去除ATRA后,继续培养1天的细胞存活率上升为89%±0.2%,而继续培养2天的细胞存活率为86.3%±1.4%;ATRA与TPA序贯分化6天细胞存活率下降为75.9±0.4%。当去除TPA后,继续培养一天的细胞存活率为75.5±0.7%,继续培养2天的细胞存活率为74.9±1.0%。结论：维甲酸（ATRA）处理和ATRA与十四烷酰佛波醇乙酸酯（TPA）序贯处理（ATRA/TPA）均能明显诱导SH-SY5Y细胞分化。这两种分化细胞为神经科学的研究提供了优良的体外培养模型细胞,尤其是ATRA与TPA序贯处理能获得分化完全而稳定的神经元样细胞。     

Insulin-like growth factor I rescues SH-SY5Y human neuroblastoma cells from hyperosmotic induced programmed cell death

Insulin-like growth factor I (IGF-I) and the type I IGF receptor are widely distributed in developing and adult mammalian nervous systems. In vitro, IGF-I is a mitogen for primary neurons and also for cells from the SH-SY5Y human neuroblastoma cell line, a well-characterized model system of neuronal growth. In the current study, we examined the effects of osmotic stress on SH-SY5Y cell viability and the mechanism by which IGF-I serves as a neuronal osmoprotectant. Within 24 hr, exposure of SH-SY5Y cells to hyperosmotic serum-free media decreased (1) the number of viable cells, (2) the rate of ³H-thymidine incorporation, and (3) cell cycle progression. The inclusion of 10 nM IGF-I with hyperosmotic media prevented the loss of cell viability. The osmoprotective effects of IGF-I were inhibited by α-IR_J, a blocking antibody of the type I IGF receptor. The observed loss of SH-SY5Y cell viability following hyperosmotic shock was due to an induction of programmed cell death as determined by flow cytometry and gel electrophoresis. Our results suggest that IGF-I can protect SH-SY5Y cells from hyperosmotic induced programmed cell death. © 1996 Wiley-Liss, Inc.     

山楂叶金丝桃苷对高糖诱导SH-SY5Y细胞损伤的保护作用及机制

为研究金丝桃苷对高糖诱导的人神经母细胞瘤(SH-SY5Y)细胞氧化损伤的保护作用及机制,用含100mmo L/L葡萄糖和分别为20、50、100μmo L/L金丝桃苷的培养基共同孵育SH-SY5Y细胞36 h,检测细胞活力、细胞培养液中乳酸脱氢酶(LDH)水平及半胱氨酸天冬氨酸蛋白酶-3(caspase-3)活性,细胞内活性氧(ROS)水平、丙二醛(MDA)、还原型谷胱甘肽(GSH)含量和超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及SIRT1和NF-кB基因的mRNA水平和蛋白含量。结果显示金丝桃苷可提高高糖诱导后SH-SY5Y细胞的存活率,抑制细胞LDH释放,清除ROS,降低MDA含量与caspase-3活性,增强SOD、CAT活性和GSH含量;同时,金丝桃苷还能提高SIRT1基因的mR-NA表达及蛋白含量,降低NF-кB基因的mRNA水平和蛋白含量。结果表明金丝桃苷能通过激活SIRT1基因,抑制NF-кB基因保护高糖所致SH-SY5Y细胞的氧化损伤。     

Apparent noncompetitive antagonism of muscarinic receptor mediated Ca2+ mobilization by some muscarinic antagonists.

Ca2+ mobilizations in SH-SY5Y and IMR-32 human neuroblastoma cell lines were measured using the fluorescent Ca2+ indicator fura-2. A variety of antagonists (atropine, pirenzepine, 4-DAMP and N-methyl-scopolamine) inhibited carbamyl choline-induced transient Ca2+ mobilization both in a competitive and a noncompetitive manner. The apparent noncompetitive inhibition constants were lower in IMR-32 than in SH-SY5Y cells even when the competitive inhibition constants were similar. This may relate to the previously reported differential expression of muscarinic receptor subtypes in these cell lines.     

Carbachol-stimulated calcium entry in SH-SY5Y human neuroblastoma cells: which route?

M3 muscarinic receptors expressed on SH-SY5Y human neuroblastoma cells are linked to phosphoinositide turnover and rises in [Ca2+]i. The rise in [Ca2+]i is biphasic with the peak phase being due to release from an intracellular Ins(1,4,5)P3-sensitive site and the plateau phase being due to Ca2+ entry across the plasma membrane. Ca2+ entry does not appear to involve voltage sensitive Ca2+ channels, a pertussis toxin sensitive G-protein-operated Ca2+ channel or Ins(1,4,5)P3/Ins(1,3,4,5)P4-operated Ca2+ channel. We suggest that carbachol-stimulated Ca2+ entry in SH-SY5Y human neuroblastoma cells occurs via receptor operated Ca2+ channels and through capacitive refilling.     

Carbonyl stress and NMDA receptor activation contribute to methylglyoxal neurotoxicity

Methylglyoxal (MG) is a reactive alpha-ketoaldehyde physiologically generated as a by-product of glycolysis. MG that is able to form protein adducts resulting in advanced glycation end products accumulates under conditions associated with neurodegeneration such as impaired glucose metabolism or oxidative stress. In the present study, short-term exposure of human neuroblastoma SH-SY5Y cells to MG was associated with an early depolarization of the plasma membrane, glutamate release, and formation of reactive oxygen species. In addition, long-term exposure (24 h) of SH-SY5Y cells to MG caused a decrease in cell viability, intracellular ATP, and rhodamine 123 (Rh-123) fluorescence. ATP depletion and the decrease in Rh-123 fluorescence were prevented by carbonyl scavengers, the nitric oxide synthase inhibitor L-NAME, and N-methyl-d-aspartate (NMDA) receptor antagonists. Furthermore, the MG-induced glutamate release and the loss in cell viability were prevented by NMDA receptor antagonists. Therefore, MG renders cells more vulnerable to excitotoxicity. In conclusion, carbonyl scavengers as well as NMDA receptor antagonists may represent effective therapeutic tools to reduce the risk of pathophysiological changes associated with carbonyl stress in neurodegenerative diseases.     

The putative somatostatin antagonist,cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), may act as potent antiproliferative agonist

The cyclic somatostatin (SST) analogue, cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]) (cSSTA), has been widely used as somatostatin antagonist. In the human neuroblastoma cell line SH-SY5Y the cyclopeptide acts as a somatostatin receptor agonist. Similar to SST, cSSTA inhibits cell proliferation, activates the protein tyrosine phosphatase SHP-2, and stimulates the activity of mitogen-activated protein kinase. These results suggest that in SH-SY5Y neuroblastoma cells somatostatin receptors may exist which exhibit altered antagonist binding properties.