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971.
972.
Lovastatin protects mesenchymal stem cells against hypoxia- and serum deprivation-induced apoptosis by activation of PI3K/Akt and ERK1/2 总被引:2,自引:0,他引:2
Cell therapy with bone marrow-derived mesenchymal stem cells (MSCs) has been shown to have great promises in cardiac repair after myocardial infarction. However, poor viability of transplanted MSCs in the infracted heart has limited the therapeutic efficacy. Our previous studies have shown in vitro that rat MSCs undergo caspase-dependent apoptosis in response to hypoxia and serum deprivation (Hypoxia/SD). Recent findings have implicated statins, an established class of cholesterol-lowering drugs, enhance the survival of cells under various conditions. In this study, we investigated the effect of lovastatin on rat MSCs apoptosis induced by Hypoxia/SD, focusing in particular on regulation of mitochondrial apoptotic pathway and the survival signaling pathways. We demonstrated that lovastatin (0.01-1 microM) remarkably prevented MSCs from Hypoxia/SD-induced apoptosis through inhibition of the mitochondrial apoptotic pathway, leading to attenuation of caspase-3 activation. The loss of mitochondrial membrane potential and cytochrome-c release from mitochondria to cytosol were significantly inhibited by lovastatin. Furthermore, the antiapoptotic effect of lovastatin on mitochondrial apoptotic pathway was effectively abrogated by both PI3K inhibitor, LY294002 and ERK1/2 inhibitor, U0126. The phosphorylations of Akt/GSK3 beta and ERK1/2 stimulated by lovastatin were detected. The activation of ERK1/2 was inhibited by a PI3K inhibitor, LY294002, but U0126, a ERK1/2 inhibitor did not inhibit phosphorylation of Akt and GSK3 beta. These data demonstrate that lovastatin protects MSCs from Hypoxia/SD-induced apoptosis via PI3K/Akt and MEK/ERK1/2 pathways, suggesting that it may prove a useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction. 相似文献
973.
Chen J Chen Y Zhu W Han Y Han B Xu R Deng L Cai Y Cong X Yang Y Hu S Chen X 《Journal of cellular biochemistry》2008,103(6):1718-1731
Lysophosphatidic acid (LPA) is a bioactive phospholipid with diverse functions mediated via G-protein-coupled receptors (GPCRs). In view of the elevated levels of LPA in acute myocardial infarction (MI) patients we have conducted studies aimed at identifying specific LPA receptor subtypes and signaling events that may mediate its actions in hypertrophic remodeling. Experiments were carried out in cultured neonatal rat cardiomyocytes (NRCMs) exposed to LPA and in a rat MI model. In NRCMs, LPA-induced hypertrophic growth was completely abrogated by DGPP, an LPA1/LPA3 antagonist. The LPA3 agonist OMPT, but not the LPA2 agonist dodecylphosphate, promoted hypertrophy as examined by 3[H]-Leucine incorporation, ANF-luciferase expression and cell area. In in vivo experiments, LPA1, LPA2 and LPA3 mRNA levels as well as LPA1 and LPA3 protein levels increased together with left ventricular remodeling (LVRM) after MI. In addition, LPA stimulated the phosphorylation of Akt and p65 protein and activated NF-kappaB-luciferase expression. Inhibitors of PI3K (wortmannin), mTOR (rapamycin), and NF-kappaB (PDTC or SN50) effectively prevented LPA-induced 3[H]-Leucine incorporation and ANF-luciferase expression. Furthermore, ERK inhibitors (U0126 and PD98059) suppressed LPA-stimulated activation of NF-kappaB and p65 phosphorylation whereas wortmannin showed no effect on NF-kappaB activation. Our findings indicate that LPA3 and/or LPA1 mediate LPA-induced hypertrophy of NRCMs and that LPA1 and LPA3 may be involved in LVRM of MI rats. Moreover, Akt and NF-kappaB signaling pathways independently implicate in LPA-stimulated myocardial hypertrophic growth. 相似文献
974.
Using Parkinson's disease as a prototype of neurodegenerative diseases, we propose applications of human stem cells in the development of therapeutics for neurodegenerative diseases. First, in vitro differentiation of human stem cells offers a versatile model for dissecting molecular interactions underlying human dopamine (DA) neuron specification, which may form a foundation for instigating regeneration of DA neurons from progenitors that reside in the brain. Second, stem cells derived from diseased cells or through genetic modification can serve as a platform for unraveling biochemical processes that lead to the cellular pathogenesis of degeneration. This may in turn serve as a template for identifying or developing therapeutics for slowing, stopping, or reversing the disease process. And finally, stem cells, particularly those induced from patients' own cells, provide a reliable source of DA neurons for cell-based therapy. 相似文献
975.
976.
贵州黔西县少数民族ABO血型分布及基因频率调查 总被引:5,自引:0,他引:5
对贵州黔西县1260例6个少数民族人群红细胞ABO表现型进行了检测;结果如下:贵州黔西县布依族、满族、苗族、白族这四个民族的ABO血型基因频率很相近,彝族和仡佬族与这4个民族的差别较大,布依族,苗族,满族,白族ABO血型分布为O>B>A>AB,彝族为O>A>B>AB,仡佬族为A>O>B>AB;经Hardy Weinberg吻合度检测可以证明贵州黔西县的ABO血型表现型分布状况及基因频率相对稳定,其分布符合hardy Weinberg平衡,获得了该地ABO血型系统群体遗传学数据,为群体遗传学的研究提供了一定的资料。 相似文献
977.
为了观察尿激酶受体(uPAR)反义核酸对肿瘤细胞体外侵袭的抑制作用,用PCR方法扩增uPAR cDNA 5′端-46 bp~+454 bp一段长500 bp的序列,利用DNA重组技术将其克隆到病毒载体pAdeno-X中, 构建出重组腺病毒载体pAdeno-X-uPAR(-)和pAdeno-X-uPAR(+).线性化后的重组腺病毒载体转染HEK293细胞7天后,可以获得滴度分别为1.5×108 pfu/ml和0.5×108 pfu/ml的uPAR反义和正义核酸表达重组腺病毒,分别命名为Ad-uPAR(-)和Ad-uPAR(+).以不同的病毒感染指数(MOI)感染人肺巨细胞癌高转移株95D肿瘤细胞,3天后用RNA印迹法可以检测肿瘤细胞uPAR正义和反义核酸表达水平,随着MOI的升高,Ad-uPAR(-)感染的肿瘤细胞uPAR蛋白水平逐渐下降,肿瘤细胞的体外侵袭能力也明显下降,而感染Ad-uPAR(+)的肿瘤细胞无明显变化.结果表明,重组腺病毒可以表达uPAR正义和反义核酸,uPAR反义核酸可以明显抑制人肺巨细胞癌高转移株95D肿瘤细胞在体外的侵袭能力. 相似文献
978.
不同烟草品种叶下表皮微形态学特征的研究 总被引:3,自引:0,他引:3
利用扫描电镜及光学显微镜对烤烟、晒烟及野生烟共29个品种叶下表皮微形态学特征进行了观察,发现相同类型的烟草品种间表现出一些共同特征,但不同类型的烟草品种间其叶下表皮微形态学特征又存在一定的差异。烤烟气孔外拱盖内缘较丰富,晒烟次之,野生烟在所观察的品种中只有1种类型;烤烟气孔密度和长度的变幅比较大,晒烟则比较稳定;烤烟、晒烟细胞间多有突起,保卫细胞极区常见“T”型加厚,绝大多数有角质环边;而所观察的两个野生烟品种均无细胞间突起,无保卫细胞极区加厚,亦无角质环边。这些观察结果为烟草分类研究提供了有价值的参考依据。同时本文还探讨了烟草亲本与子代之间在叶下表皮微形态学特征上的关联性。 相似文献
979.
香溪河流域一条一级支流河岸林凋落物季节动态 总被引:3,自引:0,他引:3
对神农架南坡的一条一级支流河岸林的凋落物进行了一年的连续收集研究。结果表明:凋落物干重年输入量为438.72g/m^2,其中树叶凋落物是凋落物的主要成分,占整个凋落物年产量的84%。凋落物的输入明显存在季节性的时间格局。凋落物在秋季的产量占全年产量的75%,春季占6.2%,夏季占13.6%,冬季为5.5%。凋落物组成中,树叶和花果的产量显示出季节变化的趋势;枝条的产量并未显示出明显的季节趋势。在秋季,树叶的产量占全年树叶总量的83%;枝条最高值出现于秋季,产量占全年总员的29%;花果在整个凋落物中所占比重分小,最高值出现在夏季,占年产量的63%。着生藻类的密度月际间的变化较大,存在着显著的差异。最大值与最小值的出现月份与凋落物最大、最低值的出现月份相同。通过统计分析表明,着生藻类的密度变化与凋落物和树叶凋落物的动态具有明显的相关性。 相似文献
980.
维生素C为6碳多羟化合物,在化学反应中易失去电子,依次生成半脱氧抗坏血酸和脱氧抗坏血酸。因此,维生素C可作为自由基清除剂,能迅速与超氧阴离子、氢化氧基、过氧化氢、羟自由基反应,生成抗坏血酸自由基。蓝光作为一种短波长,靠近紫外线频段的光,具有能量高的特点,是自然界中导致视网膜色素上皮细胞损伤甚至凋亡的主要光线。本实验通过观察蓝光照射视网膜色素上皮,对其DNA的损伤产生光损伤作用,并比较加入维生素C后对这种光损伤的保护作用,以期探讨维生素C在 相似文献