神经酰胺信使途径

生物体内神经酰胺有多种生成途径。作为重要的第二信使,神经酰胺在多种信号转导过程中发挥广泛作用,从而影响细胞生长、增殖、分化、凋亡及损伤等多种生理、病理过程。此机制的发现被认为是近年来信号转导研究的重要进展之一。     

神经酰胺：细胞凋亡信号转号的第二信使分子

神经酰胺是细胞凋亡信号调控中的一个第二信使因子,许多应激刺激能激活神经鞘磷脂循环产生神经酰胺诱导多种细胞体系发生凋亡。神经酰胺介导细胞凋亡的机理尚未完全明了,可能是通过多个下游靶分子包括ＣＡＰＫ,ＣＡＫＫ,ＰＫＣ,ＳＡＰＫ／ＪＮＫ,ＣＰＰ３２,Ｂｃｌ－２以及Ｒａｓ－ＲａｃｌＪＮＫ／ｐ３８－Ｋ→ＧＡＤＤ１５３信号传导链等作用于不同的信号转导途径而诱导细胞凋亡的。     

第二信使神经酰胺

第二信使神经酰胺丁振华（第一军医大学基础部,广州５１０５１５）关键词第二信使神经酰胺鞘磷脂酶１９９５年,Ｂｏｕｃｈｅｒ及其同事发现,在原代培养的小鼠脾Ｔ淋巴细胞中,ＣＤ２８的信号传导能够通过鞘磷脂（ｓｐｈｉｎｇｏｍｙｌｉｎ）通路而活化核因子ＮＦ－κＢ...     

紫外照射神经酰胺的生成及神经酰胺引起的细胞凋亡

参照文献报道的方法建立了测定细胞神经酰胺的激酶催化法,以该法所做的标准曲线在一定浓度范围内有很好的线性关系。以ＵＶＢ照射ＮＩＨ ３Ｔ３细胞,可以使细胞神经酰胺的水平在１分钟之内迅速升高１．５倍以上,基本上达到了细胞所能生成神经酰胺的最高峰值。可细胞膜的外源性神经酰胺（Ｃ２－ｃｅｒａｍｉｄｅ）作用于ＮＩＨ ３Ｔ３细胞后能够导致细胞的凋亡和坏死,其凋亡率在一定剂量范围内随神经酰胺浓度的增加而增加;而在     

神经酰胺与细胞凋亡

神经酰胺与细胞凋亡叶珉王亚新（上海第二医科大学附属瑞金医院血液学研究所,上海２０００２５）关键词神经酰胺细胞凋亡信号转导细胞凋亡为维持机体内环境稳定所必需,它与有丝分裂相互协调,共同调控胚胎发育、器官的发育和退化、免疫和造血等功能。研究发现,神经酰胺...     

神经酰胺在细胞调亡中的作用

本从神经酰胺的代谢,神经酰胺在神经鞘磷酯途径中充当第二信使,神经鞘磷酯途径连接SAPK／JNK（stress-activated Protein kinase/c-Jun N-terminal protein kinase)凋亡信号转导途径,神经酰胺介导的凋亡信号途径与ICE／Ced-3蛋白激酶的相互作用这四个方面阐述了神经酰胺在介导细胞凋亡中所起的中心作用,以利于了解促进,抑制凋亡的机制及其协同机制,为进一步的研究打好理论基础.     

神经酰胺激酶(CerK)催化反应的肿瘤生物学意义

神经酰胺激酶(ceramide kinase,CerK)是唯一已知的在哺乳动物细胞中催化神经酰胺(ceramide,Cer)磷酸化为1-磷酸神经酰胺(ceramide-1-phosphate,C1P)的脂蛋白酶.作为该酶促反应底物的Cer在神经鞘脂代谢和信号转导途径中起着中心介质的作用,调节许多基础的细胞反应;而C1P...     

UVB诱导NIH3T3细胞凋亡时的信号转导机制:Ⅱ.神经酰胺所致细胞内Ca~(2+)和pH的变化

利用粘附式细胞仪（ＡＣＡＳ－５７０）结合相应的荧光探针分别测定了外源性神经酰胺诱导ＮＩＨ３Ｔ３细胞凋亡时胞浆游离Ｃａ＾２＋水平和ＵＶＢ照射ＮＩＨ ３Ｔ３细胞所致细胞内ＰＨ的变化以及神经酰胺的生民对这一变化的影响。结果表明,１．神经酰胺能够导致ＮＩＨ ３Ｔ３细胞胞浆游离Ｃａ＾２＋升高既来源于胞外叠为源于胞内钙池,但外钙内流是引起和维持胞内Ｃａ＾２＋处于高水平所必要条件,ＮＩＨ ３Ｔ３细胞也上存在着两     

神经酰胺与细胞凋亡

细胞凋亡 (apoptosis) 又称细胞的程序性死亡,参与机体许多生理和病理过程.近年来的研究表明细胞凋亡与鞘脂质代谢有密切的关系,鞘磷脂的水解产物神经酰胺作为脂质第二信使在诱导和抑制细胞凋亡中起着重要的作用.     

Ceramide: physiological and pathophysiological aspects

Ceramide generated in the cell membrane has been shown to be central for the induction of apoptosis by death receptors and many stress stimuli such as gamma-irradiation, UV-light or infection with pathogens. Ceramide reorganizes cell membranes and forms large ceramide-enriched membrane domains that serve the spatial and temporal organization of the cellular signalosome upon activation. Thus, ceramide-enriched membrane domains mediate clustering of CD95 and DR5 to facilitate apoptosis, and they are also critically involved in apoptosis after irradiation, UV-light and infection with Pseudomonas aeruginosa. Since ceramide-enriched membrane domains amplify signals, their function is not restricted to the induction of apoptosis and it was shown that ceramide-enriched membrane domains are also involved in internalization of pathogens and the control of cytokine release from infected epithelial cells. Recent studies support the notion that changes of the ceramide metabolism are also critically involved in human diseases, for instance neurological disorders, cancer, infectious diseases and Wilson's disease.     

Ionic regulation of cyclic AMP levels in Paramecium tetraurelia in vivo

cAMP levels in Paramecium increased dose dependently after a step increase of [Ca] or [Sr] in the incubation, provided K was present. Two mM Ca or Sr tripled cAMP concentrations within 3 s and induced an increase in forward swimming speed. The increase in cAMP formation was strictly dependent on the Donnan ratio [K]: square root [Ca]. Na, Li, or tetraethylammonium could not replace K. The data provide evidence for regulation of cAMP in Paramecium by the membrane surface charge as determined specifically by the regulation of cAMP in Paramecium by the membrane surface charge as determined specifically by the K: Ca ratio.     

脱落酸信号转导研究进展

脱落酸（ABA）对植物生长发育和适应环境胁迫等多方面有重要的调节作用,其信号转导机制非常引人注目,近年来这方面研究进展很快,本文利用现有文献,对脱落酶不敏感和超敏感性突变体,脱落酸的结合位点与受体,ABA信号转涉及的细胞第二信使（Ca^2 ,磷酸肌醇,cADPR,阴离子通道与H^ ), 蛋白质可逆磷酸化以及ABA诱导基因表达所必需的顺序作用元件（cis-acting elenment)和反式作用因子（trans-acting factor)等几方面的最新研究进展作了介绍。     

Entirely Artificial Signal Transduction with Adrenaline

Multifunctional transmembrane-building blocks with recognition sites for adrenaline on one end and the reaction partners for an S_N2 reaction on the opposite end have been embedded in DPPC-liposomes. These doped vesicles can be quantitatively reduced at their disulfide head groups by externally added reducing agents; their composition and chemical processes taking place within can be monitored by NMR spectroscopy and–with limitations—by UV/Vis spectroscopy. Attempted release of thiopyridine as a second messenger into the interior of the liposome on external adrenaline addition could not be proven unambiguously because the detection system does not fulfill the necessary rigorous specificity and sensitivity requirements.     

丹皮酚通过酸性鞘磷脂酶/ 神经酰胺通路改善血管紧张素II 所致动脉内 皮功能障碍

目的:探讨丹皮酚(Paeonol,Pae)对血管紧张素II(AngiotensinⅡ,AngⅡ)所致动脉内皮功能障碍的保护作用及其机制。方法:采用实时定量聚合酶链式反应(RT-PCR)和Westernblot检测酸性鞘磷脂酶(acidsphingomyelinase,ASM)基因及蛋白表达;采用免疫组织荧光检测血管环神经酰胺(ceramide,Cer)含量变化;采用血管环张力描记技术检测主动脉血管环的舒张功能;采用二氢乙啶荧光探针(dihydroethidium,DHE)检测血管环超氧阴离子(superoxideanion,O2-·)水平。结果:与对照组相比,AngⅡ孵育后主动脉对乙酰胆碱(acetylcholine,Ach)的舒张反应显著降低,Pae与AngⅡ共孵育则无明显改变;AngⅡ及Pae孵育后,动脉对硝普钠(sodiumnitroprusside,SNP)的舒张反应均无明显变化;AngⅡ孵育可增高动脉环O2-·水平,这一反应被Pae明显抑制;与对照组相比,AngⅡ孵育动脉ASMmRNA水平无明显改变,但蛋白表达显著增加,Cer含量显著增多,Pae与AngⅡ共孵育动脉ASM蛋白及Cer水平与对照组相比均无明显改变;采用神经酰胺酶抑制剂N-oleoylethanolamine(OEA)增加动脉Cer含量后,Pae降低动脉O2-·水平以及增强Ach舒张反应的效应被显著抑制。结论:Pae通过ASM/Cer通路改善AngⅡ所致动脉氧化应激增强和内皮功能障碍。     

Staurosporine Induces Programmed Cell Death in Embryonic Neurons and Activation of the Ceramide Pathway

Abstract: We activated the death pathway in embryonic chick cerebral hemisphere neuron (E7CH) cultures with staurosporine (0.1–1.0 µ M ) and observed the morphological changes, DNA laddering patterns, and DNA fragmentation (determined by Hoechst 33258 dye) associated with apoptosis. N -Acylsphingosine (C2-ceramide), a soluble ceramide analogue, was also able to induce apoptosis in these cells with the same characteristics and in the same time frame. We then observed that staurosporine was effective in inducing hydrolysis of sphingomyelin to ceramide as measured by a threefold increase in ceramide mass and increased incorporation of [³H]-palmitate into ceramide, concurrent with activating the cell death program. Furthermore, the coaddition of a specific ceramidase inhibitor, oleoylethanolamine (15 µ M ), enhanced the formation of ceramide as well as the degree of DNA fragmentation and cell death. Exogenous addition of sphingomyelinase activated the death pathway whereas ceramide glycanase did not, and inhibitors of sphingomyelin or protein synthesis failed to block this type of killing. Our data suggest that the formation of ceramide from sphingomyelin is a key event in staurosporine-induced and potentially all programmed cell death.     

Ceramide biosynthesis in keratinocyte and its role in skin function

The enucleate layer of the epidermis, i.e. the stratum corneum, is responsible for certain critical protective functions, such as epidermal permeability barrier function. Within the epidermal membrane lamella component, ceramides are the dominant lipid class by weight (over 50%) and exhibit the greatest molecular heterogeneity in terms of sphingoid base and fatty acid composition. It is now evermore important to understand how ceramide production and functions are controlled in the epidermis, since decreased epidermal ceramide content has been linked to water loss and barrier dysfunction. During the past several years, critical enzymes in ceramide biosynthesis have been identified, including ceramide synthases (CerS) and ceramide hydroxylase/desaturase. In this review, we describe the molecular heterogeneity of ceramides synthesized in the epidermis and their possible roles in epidermal permeability barrier functions. We also describe recent studies that identified the family of CerS (CerS1–CerS6) in mammals. We further focus on the roles of specific isoforms of these enzymes in synthesizing the epidermal ceramides, especially in relation to chain-length specificity. In addition, we provide experimental information, including our recent findings, as to how applying ceramide or ceramide-containing substances to skin, orally or directly, can benefit skin health.     

UVB诱导NIH 3T3细胞凋亡时的信号转导机制:Ⅱ.神经酰胺所致细胞内Ca2+和pH的变化

利用粘附式细胞仪 (ACAS -570)结合相应的荧光探针分别测定了外源性神经酰胺诱导NIH3T3细胞凋亡时胞浆游离Ca2 水平和UVB照射NIH3T3细胞所致细胞内 pH的变化以及神经酰胺的生成对这一变化的影响。结果表明 :1.神经酰胺能够导致NIH3T3细胞胞浆游离Ca2 升高 ;胞浆Ca2 升高既来源于胞外钙 ,又来源于胞内钙池 ,但外钙内流是引起和维持胞内Ca2 处于高水平的必要条件 ;NIH3T3细胞钙池上存在着两种受体 :IP3 受体和Ryanodine受体 ,其中IP3受体较占优势。2.UVB照射导致NIH3T3细胞凋亡时胞浆碱化并持续约2小时左右恢复正常 ,pH的变化参与了细胞凋亡的过程并受到神经酰胺生成的调控。这可能是UVB照射启动了磷脂肌醇通路激活磷脂酶C ,导致神经酰胺的生成、Ca2 动员和蛋白激酶C的活化 ,从而激活Na /H 对流引起胞浆碱化。所以 ,胞浆游离Ca2 的增加和 pH的升高不是两个孤立的事件。