Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis

The present study reports for the first time a dual antiglioma effect of the well-known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma cell line, metformin blocked the cell cycle progression in G₀/G₁ phase without inducing significant cell death. In confluent C6 cultures, on the other hand, metformin caused massive induction of caspase-dependent apoptosis associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial depolarization and oxidative stress. Metformin-triggered apoptosis was completely prevented by agents that block mitochondrial permeability transition (cyclosporin A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided partial protection. The antiglioma effect of metformin was reduced by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK agonist AICAR. Similar effects were observed in the human glioma cell line U251, while rat primary astrocytes were completely resistant to the antiproliferative and proapoptotic action of metformin. Received 14 February 2007; received after revision 26 March 2007; accepted 3 April 2007     

The mitochondrial function was impaired in APP knockout mouse embryo fibroblast cells

The amyloid precursor protein (APP) is recognized as the source of Aβ, which plays an important role in Alzheimer’s disease. However, the biological function of APP is obscure. Previous studies showed that mitochondria could be a target of APP. In this work, APP knockout mouse embryo fibroblast (MEF) cells were used to test if APP plays any role in maintaining the mitochondrial function. As the result, APP knockout MEF cells (APP-/- cells) showed the abnormal mitochondrial function, including slower cell pr...     

疣尾蜥虎线粒体基因组全序列及其基因组成

测定了疣尾蜥虎(Hemidactylus frenatus) 的线粒体基因组全序列.序列全长为16 891 bp, 包括13 个蛋白质编码基因、2 个rRNA 基因和22 个tRNA 基因.除大部分基因由重链编码外,仅1个蛋白编码基因和8个tRNA基因由轻链编码.碱基组成的偏好与其他脊椎动物线粒体DNA接近.没有发现长的基因间隔区,说明该基因组的结构十分紧凑.基因组的组成与典型脊椎动物的相近,即没有发现重排、基因或控制区的重复等在其它有鳞类动物中出现过的异常特征.除单性生殖的壁虎外,现有的壁虎类线粒体基因组在基因含量和顺序上是一致的.作为蜥虎属线粒体基因组全序列的惟一代表,该序列有望在有鳞类系统发生的推断上发挥一定的作用.     

暗纹东方鲀线粒体ATPase8和ATPase6基因的克隆与序列分析

克隆并测定了暗纹东方鲍（Takifugu fasciatus）线粒体ATP合酶Fo亚基8（ATPase8）和亚基6（ATPase6）的序列,并对其进行了初步分析。结果表明：PCR扩增产物的总长度为923bp,其中842bp为ATP8和ATP6基因的编码区。ATP8基因长168bp,编码55个氨基酸残基的蛋白质,其蛋白分子质量为6．8KD,等电点为7．85;ATP6基因长684bp,编码227个氨基酸残基的蛋白质,其蛋白分子质量为24．9KD,等电点为9．16。暗纹东方纯ATP合酶Fo亚基8和亚基6与其他已报道的部分东方纯属鱼类具有很高的同源性。通过探讨ATP合酶F0亚基所含的信息量,发现相对于其他线粒体基因,ATPase8和ATPase6基因所含鉴别信息较少。     

瑞舒伐他汀钙干预对高尿酸血症所致大鼠内皮功能紊乱的影响

 为探讨瑞舒伐他汀钙(rosuvastatin)对高尿酸血症大鼠模型及其内皮功能紊乱的影响,将72只Sprague-Dawley(SD)雄性大鼠随机分组,采用酵母膏和氧嗪酸钾腹腔注射方法,建立高尿酸血症动物模型.设别嘌呤醇干预为阳性对照,以2.5、5.0和10.0mg瑞舒伐他汀钙/kg剂量干预动物模型,采用专用试剂盒测定尿酸(UA)、一氧化氮(NO)、内皮素-1(ET-1)、血管紧张素II(AngII)的血清水平,免疫组织化学鉴定主动脉组织的一氧化氮合酶(eNOS)蛋白质表达水平变化.结果显示,与对照组比较,高尿酸血症动物模型组血清UA、ET-1和AngII显著升高,血清NO降低,主动脉内皮组织eNOS表达水平降低.瑞舒伐他汀钙干预动物模型后发现,随着药物剂量和干预时间的增加,该药改善以上内皮功能紊乱相关的指标,使之逐渐恢复至正常水平,当瑞舒伐他汀钙干预剂量为10mg/(kg·d)和干预6周时,与非药物干预的模型组有显著差异,其改善内皮功能效果明显高于嘌呤组(阳性对照组).由此表明,瑞舒伐他汀钙通过升高血清中NO和eNOS的蛋白表达,降低血浆ET-1及AngII,从而改善高尿酸血症大鼠的血管内皮功能,并且该作用呈剂量依赖性.     

高容量血液滤过治疗严重颅脑损伤后多器官功能障碍的研究

探讨高容量血液滤过治疗严重颅脑损伤后多器官功能障碍患者的预后及与肿瘤坏死因子(TNF-α)、白介素-1、白介素-10水平的变化。无肝素化血液滤过治疗重度颅脑损伤多脏器衰竭患者,监测病人14 d死亡率及监测病人、24 h、48 h TNF-α、IL-1、IL-10变化。结果血液滤过治疗24 h及48 h的TNF-α、IL-1、IL-10水平明显低于血滤治疗前。治疗14 d后治疗组死亡率明显低于对照组。高容量血液滤过治疗严重颅脑损伤后多器官功能障碍的患者,能够降低炎症介质改善其预后。     

古代契丹与现代达斡尔遗传关系分析

对23个契丹人骨样本线粒体第一高可变区(364 bp)进行了扩增和测序, 得到22个不同序列. 构建了契丹、 达斡尔及对比人群的系统发育树, 结果明, 契丹与外蒙的遗传关系最近, 与达斡尔的遗传关系也较近; 契丹与达斡尔的序列在突变位点和突变率上存在较大差异. 表明虽然契丹与达斡尔之间存在较近的亲缘关系, 但达斡尔不一定是契丹的直接后裔.     

Bacterial signal peptide recognizes HeLa cell mitochondrial import receptors and functions as a mitochondrial leader sequence

Phage display was used to identify new components of the mammalian mitochondrial receptor complex using Tom20 as a binding partner. Two peptides were identified. One had partial identity (SMLTVMA) with a bacterial signal peptide from Toho-1, a periplasmic protein. The other had partial identity with a mitochondrial inner membrane glutamate carrier. The bacterial signal peptide could carry a protein into mitochondria both in vivo and in vitro. The first six residues of the sequence, SMLTVM, were necessary for import but the two adjacent arginine residues in the 30-amino-acid leader were not critical for import. The signal peptides of Escherichia coli β-lactamase and Bacillsus subtilis lipase could not carry proteins into mitochondria. Presumably, the Toho-1 leader can adopt a structure compatible for recognition by the import apparatus.Received 29 April 2005; received after revision 8 June 2005; accepted 17 June 2005     

Mitochondrial DNA analysis of Bronze Age horses recovered from Chifeng region, Inner Mongolia, China

In this study, mitochondrial DNA (mtDNA) analysis was carried out on 9 Bronze Age horses recovered from Dashanqian and Jinggouzi archaeological sites in Chifeng region, Inner Mongolia. China to explore the origin of Chinese domestic horses. Both mtDNA 16S rRNA gene and control region (D-loop) fragments of ancient horses were amplified and sequenced. The analysis of the highly conservative 16S rRNA gene sequences indicated that the burial environment of Chifeng region is suitable for the preservation of ancient DNA (aDNA). Combing 465 mtDNA D-loop sequences representing different breeds from East Asia, Central Asia, Near East and Europe, we constructed a phylogenetic network to investigate the relationship between ancient and modern horses. The phylogenetic network showed that the 9 horses were distributed into different modern horse clusters which were closely related to them representing a certain geographical distribution. Our results showed that the maternal genetic line of the ancient horses in Chifeng region was highly diversified, which contributed to the gene pool of modern domestic horses and suggested a complex origin of domestic horses in China.     

Mitochondrial DNA analysis of ancient Sampula population in Xinjiang

The archaeological site of Sampula cemetery was located about 14 km to the southwest of the Luo County in Xinjiang Khotan,China,belonging to the ancient Yutian kingdom.~14C analysis showed that this cemetery was used from 217 B.C.to 283 A.D. Ancient DNA was analyzed by 364 bp of the mitochondrial DNA hypervariable region I (mtDNA HVR-I),and by six restriction fragment length polymorphism (RFLP) sites of mtDNA coding region.We successfully extracted and sequenced intact stretches of maternally inher- ited mtDNA from 13 out of 16 ancient Sampula samples.The analysis of mtDNA haplogroup distribution showed that the ancient Sampula was a complex population with both European and Asian characteristics.Median joining network of U3 sub-haplogroup and multi-dimen- sional scaling analysis all showed that the ancient Sampula had maternal relationship with Ossetian and Iranian.