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The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading to Leber's hereditary optic neuropathy (LHON). Despite considerable clinical evidences, the modifier role of nuclear background and mitochondrial haplotypes in phenotypic manifestation of LHON remains poorly understood. We investigated the effect of these modifiers on bioenergetics in lymphoblastoid cell lines derived from five affected subjects of one Chinese family carrying the G11778A mutation and five Chinese controls. Significant reductions in the activities of complexes I and III were observed in mutant cell lines from the Chinese family, whereas the mutant cell lines from other families carrying the same mutation exhibited only reduced activity of complex I. The reduced activities of complexes I and III caused remarkably higher reductions of ATP synthesis in mutant cell lines from the Chinese family than those from other families. The deficient respiration increased generation of reactive oxygen species. The defect in complex III activity, likely resulting from the mitochondrial haplotype or nuclear gene alteration, worsens mitochondrial dysfunction caused by the G11778A mutation, thereby causing extremely high penetrance and expressivity of optic neuropathy in this Chinese family. Our data provide the first experimental evidence that altered activity of complex III modulates the phenotypic manifestation of LHON-associated G11778A mutation. Thus, our findings may provide new insights into the pathophysiology of LHON. 相似文献
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多胞质玉米胚乳淀粉粒性状的扫描电镜观察 总被引:8,自引:0,他引:8
11种多胞质系玉米胚乳淀粉粒的扫描电镜观察表明:不同的细胞质对细胞核有不同程度的互作,3种甜质胞质玉米的胚乳淀粉粒多呈球形,排列紧密,存在一定的共性;4种雄性不育胞质玉米的胚乳淀粉粒多呈不规则形,除(T)Mo17外,排列疏松。这11种玉米胚乳淀粉粒的平均直径为9.78μm ̄14.69μm,通过玉米胚乳淀粉粒形态特征的观察,在玉米淀粉性状和玉米籽粒的商品价值关系上进行一定程度探索,为玉米的进一步发展 相似文献
36.
To investigate the effect of human pyruvate carboxylase (hPC) on lactate formation in Chinese hamster ovary (CHO) cell lines,
FLAG-tagged hPC was introduced into a dihydrofolate-deficient CHO cell line (DG44). Three clones expressing high levels of
hPC, determined by Western blotting using an anti-FLAG monoclonal antibody, and a control cell line were established. Immunocytochemistry
revealed that a substantial amount of expressed hPC protein was localized in the mitochondria of the cells. hPC expression
did not impair cell proliferation. Rather, it improved cell viability at the end of adherent batch cultures with the serum-containing
medium probably because of reduced lactate formation. Compared with control cells, specific lactate production rate of the
three clones was decreased by 21–39%, which was because of a decreased specific glucose uptake rate and yield of lactate from
glucose. Reduced lactate formation by hPC expression was also observed in suspension fed-batch cultures using a serum-free
medium. Taken together, these results demonstrate that through the expression of the hPC enzyme, lactate formation in CHO
cell culture can be efficiently reduced. 相似文献
37.
Sun M Li Z Gui JF 《Journal of experimental zoology. Part A, Ecological genetics and physiology》2010,313(8):461-473
Spindlin (Spin) was thought as a maternal-effect factor associated with meiotic spindle. Its role for the oocyte-to-embryo transition was suggested in mouse, but its direct evidence for the function had been not obtained in other vertebrates. In this study, we used the CagSpin-specific antibody to investigate CagSpin expression pattern and distribution during oogenesis of gibel carp (Carassius auratus gibelio). First, the oocyte-specific expression pattern and dynamic distribution was revealed in nucleoli, nucleoplasm, and spindle from primary oocytes to mature eggs by immunofluorescence localization. In primary oocytes and growth stage oocytes, CagSpin accumulates in nucleoli in increasing numbers along with the oocyte growth, and its disassembly occurs in vitellogenic oocytes, which implicates that CagSpin may be a major component of a large number of nucleoli in fish growth oocytes. Then, co-localization of CagSpin and β-tubulin was revealed in meiotic spindle of mature egg, indicating that CagSpin is one spindle-associated factor. Moreover, microinjection of CagSpin-specific antibody into the fertilized eggs blocked the first cleavage, and found that the CagSpin depletion resulted in spindle assembly disturbance. Thereby, our study provided the first direct evidence for the critical oocyte-to-embryo transition function of Spin in vertebrates, and confirmed that Spin is one important maternal-effect factor that participates in oocyte growth, oocyte maturation, and oocyte-to-embryo transition. 相似文献
38.
Sachs PC Francis MP Zhao M Brumelle J Rao RR Elmore LW Holt SE 《Cell and tissue research》2012,349(2):505-515
The discovery of adipose-derived stromal cells (ASCs) has created many opportunities for the development of patient-specific cell-based replacement therapies. We have isolated multiple cell strains of ASCs from various anatomical sites (abdomen, arms/legs, breast, buttocks), indicating widespread distribution of ASCs throughout the body. Unfortunately, there exists a general lack of agreement in the literature as to their "stem cell" characteristics. We find that telomerase activity and expression of its catalytic subunit in ASCs are both below the levels of detection, independent of age and culturing conditions. ASCs also undergo telomere attrition and eventually senesce, while maintaining a stable karyotype without the development of spontaneous tumor-associated abnormalities. Using a set of cell surface markers that have been promoted to identify ASCs, we find that they failed to distinguish ASCs from normal fibroblasts, as both are positive for CD29, CD73 and CD105 and negative for CD14, CD31 and CD45. All of the ASC isolates are multipotent, capable of differentiating into osteocytes, chondrocytes and adipocytes, while fibroblasts show no differentiation potential. Our ASC strains also show elevated expression of genes associated with pluripotent cells, Oct-4, SOX2 and NANOG, when compared to fibroblasts and bone marrow-derived mesenchymal stem cells (BM-MSCs), although the levels were lower than induced pluripotent stem cells (iPS). Together, our data suggest that, while the cell surface profile of ASCs does not distinguish them from normal fibroblasts, their differentiation capacity and the expression of genes closely linked to pluripotency clearly define ASCs as multipotent stem cells, regardless of tissue isolation location. 相似文献
39.
Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity 总被引:2,自引:0,他引:2
Ding M Feng R Wang SY Bowman L Lu Y Qian Y Castranova V Jiang BH Shi X 《The Journal of biological chemistry》2006,281(25):17359-17368
Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo. 相似文献