Cardiolipin, the heart of mitochondrial metabolism

Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is synthesized from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. After primary synthesis, the mature acyl chain composition of cardiolipin is achieved by at least two remodeling mechanisms. In the mitochondrial membrane cardiolipin plays an important role in energy metabolism, mainly by providing stability for the individual enzymes and enzyme complexes involved in energy production. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process and in mitochondrial membrane dynamics. Cardiolipin alterations have been described in various pathological conditions. Patients suffering from Barth syndrome have an altered cardiolipin homeostasis caused by a primary deficiency in cardiolipin remodeling. Alterations in cardiolipin content or composition have also been reported in more frequent diseases such as diabetes and heart failure. In this review we provide an overview of cardiolipin metabolism, function and its role in different pathological states. Received 16 January 2008; received after revision 26 February 2008; accepted 26 March 2008     

Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006     

Two tyrosines in CD3ε-ITAM are required to induce T lymphocyte apoptosis

CD3ε of T cell antigen receptor complex (TCR/CD3) plays an important role in the resembling of the complex and activation signaling through its conservative immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic tail. Previous study showed that a chimera molecule, consisting of the extracellular-transmembrane domain of human CD8α fused to the cytoplasmic domain of CD3ε, induced apoptosis of T lymphocytes, indicating that apoptotic signals were transduced through the CD3ε- ITAM. To elineate involvement of the two tyrosines in apoptotic signaling pathway, cDNAs with mutations at Y170F, Y181F and Y170F/Y181F in CD8-ε-ITAM were made by point mutation and PCR, and then cloned into pcDNA3 eukaryotic expression vectors. Stable expression cell lines were established after transfection of the expression vectors into CD8+- Jurkat T lymphocytes. Stimulation of these cell lines with anti-CD8 monoclonal antibody showed that only the cells with expression of wild type chimera CD8-ε died by apoptosis, but not those cells with expressions of mutated CD8-ε chimera, indicating that the two tyrosines in CD3ε-ITAM were required for the apoptotic signal transduction in T lymphocytes.     

云芝多糖在NO诱导的巨噬细胞凋亡中的分子基础

在应用云芝多糖的基础上,用NO诱导居噬细胞凋亡,发现云芝多糖可加强NO诱导的细胞凋亡;通过RT－PCR观察诱导生性一氧化氮合酶基因的表达情况,结果表明云芝多糖能诱导一氧化氮合酶基因表达,并可增强γ干扰纱和脂多糖的诱导作用,提示云芝多糖在动脉粥样硬化中的防治作用是通过诱导诱生性一氧化氮合酶表达而实现的。     

细胞凋亡与肿瘤治疗

细胞凋亡与许多疾病特别是肿瘤的发生发展有关，许多癌基因与抑癌基因参与细胞凋亡过程。对细胞凋亡以及在肿瘤治疗中的有关系进行了综述。     

微波对K562/MDR细胞凋亡及热休克蛋白70表达的影响

研究微波引起白血病耐药细胞株K562／MDR的凋亡以及对热休克蛋白70表达的影响。使用MTT方法检测细胞存活率，AnnexinV/PI双参数法检测K562／MDR细胞的凋亡率，流式细胞仪检测热休克蛋白70的表达。结果表明，微波可起K562／MDR细胞的凋亡，经0.20,0.60W/cm^2功率密度微波作用20min（保持43℃），37℃培养24h后，细胞凋亡率分别为10％、13．6％，而水浴加热引起的凋亡率仅为3．8％，微波照射影响细胞内热休克蛋白70的表达，在43℃时，0.20,0.60W/cm^2功率密度微波作用20min抑制HSP70的表达，实验说明微波能引起K562／MDR细胞的凋亡，该凋亡与微波引起的热休克蛋白表达的改变可能有联系。     

纳洛酮对大鼠脑外伤后神经细胞凋亡的影响

目的：采用Feeney法自由落体撞击脑损伤动物模型，观察纳洛酮对脑外伤后神经细胞凋亡和脑水肿的影响。方法：90只大鼠分为实验组及对照组，在损伤后15、60min及24h分别予纳洛酮或生理盐水，损伤后第5d断头处死大鼠，TUNEL法测定神经细胞原位凋亡情况，测定损伤侧大脑半球含水理以及光镜下观察细胞形态学改变。结果：与对照组比较，大鼠脑外伤后15及60min静注纳洛酮可保护神经细胞，减少凋亡率，减轻脑水肿；而外伤后24h给药，神经细胞凋亡率以及脑水肿无显著性差异。结论；研究结果提示纳洛酮作为阿片受体的拮抗剂有保护大鼠脑外伤后神经细胞的作用，但应在外伤后尽早用药。