Guoqiang Wu

Second Military Medical University, Shanghai, Shanghai, Shanghai Shi, China

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Publications (15)20.35 Total impact

  • Article: Regulation of the beta1,4-Galactosyltransferase I promoter by E2F1.
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    ABSTRACT: Cell surface carbohydrate chains are widely known to contribute to cell migration, recognition and proliferation. beta1,4-Galactosyltransferase I (beta1,4GalT I) transfers galactose to the terminal N-acetylglucosamine of complex-type N-glycan, and contributes to cell proliferation, differentiation and migration. Here, we identified beta1,4GalT I as a novel target gene of cell cycle regulator E2F1. E2F1 proteins interact with the promoter of the beta1,4GalT I gene in vivo, and E2F1 over-expression stimulates the activity of beta1,4GalT I promoter and the mRNA and protein expression of beta1,4GalT I, and augments the level of beta1, 4-galactosyltion. Site-specific mutagenesis revealed that this region which contains two E2F1 binding site (nt -215 to -207 and +1 to +6) is necessary for beta1,4GalT I activation by E2F1. Furthermore, down-regulation of beta1,4GalT I expression attenuates E2F1-induced DNA synthesis and cell cycle progression as well as the expression of cell-cycle regulator Cyclin D1. Thus, beta1,4GalT I is an important E2F1 target gene that is required for cell cycle progression in mammalian cells, which elicits a new mechanism of cell growth and a new mechanism of beta1,4GalT I transcription.
    Journal of biochemistry 09/2010; 148(3):263-71. · 1.95 Impact Factor
  • Article: Alpha2,3-Sialylation regulates the stability of stem cell marker CD133.
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    ABSTRACT: CD133 is widely used as a marker for the isolation and characterization of normal and cancer stem cells. The dynamic alternation of CD133 glycosylation contributes to the isolation of normal and cancer stem cells, and is supposed to be associated with cell differentiation. Although CD133 has been identified as a N-glycosylated protein, the specific glycosylation status of CD133 remain unclear. Here, we found that CD133 could be sialylated in neural stem cells and glioma-initiating cells, and the sialyl residues attach to CD133 N-glycan terminal via alpha2,3-linkage. Furthermore, desialylation of CD133 by neuraminidase specifically accelerates its degradation in lysosomes-dependent pathway. Taken together, our results characterized CD133 as an alpha2,3-sialylated glycoprotein and revealed that the sialylation modification contributes to the stability of CD133 protein, providing clues to understanding the function of CD133 molecular and to understanding the utility of glycosylated CD133 epitopes in defining neural stem cells and tumour-initiating cells.
    Journal of biochemistry 09/2010; 148(3):273-80. · 1.95 Impact Factor
  • Article: Identification and characterization of the promoter of human ATF5 gene.
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    ABSTRACT: ATF5, a member of ATF/CREB family of b-ZIP transcription factors, is highly expressed in a wide variety of neoplasms and regulates cell differentiation, cell survival and apoptosis. However, the mechanism of human ATF5 transcriptional regulation has not been clarified. Here, we identified the transcription start site of the ATF5 gene, cloned its 5'-flanking region and identified the region -105 to +3 relative to the transcription start site as that having promoter activity. This region contained potential binding sites for several transcription factors, including EBF1, Sp1 and E2F1. EBF1 transcription factor binds to the ATF5 promoter and regulates the ATF5 transcription in an EBF-binding site independent manner. Thus, our studies not only provided molecular basis of ATF5 transcriptional regulation, but also identified ATF5 as a target gene of EBF1 transcription factor.
    Journal of biochemistry 08/2010; 148(2):171-8. · 1.95 Impact Factor
  • Article: Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells.
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    ABSTRACT: Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.
    Biochemical and Biophysical Research Communications 07/2010; 397(4):711-7. · 2.48 Impact Factor
  • Article: Beta1,4-galactosyltransferase V regulates self-renewal of glioma-initiating cell.
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    ABSTRACT: Glioma results from unregulated expansion of a self-renewing glioma-initiating cell population. The regulatory pathways which are essential for sustaining the self-renewal of glioma-initiating cells remain largely unknown. Cell surface N-linked oligosaccharides play functional roles in determining cell fate and are associated with glioma malignancy. Previously, we have reported that beta1,4-galactosyltransferase V (beta1,4GalT V) effectively galactosylates the GlcNAcbeta1-->6Man arm of the highly branched N-glycans and positively regulates glioma cell growth. Here, we show that decreasing the expression of beta1,4GalT V by RNA interference in glioma cells attenuated the formation of polylactosamine and inhibited the ability of tumor formation in vivo. Down-regulation of beta1,4GalT V depleted CD133-positive cells in glioma xenograft, and inhibited the self-renewal capacity and the tumorigenic potential of glioma-initiating cells. These data reveal a critical role of beta1,4GalT V in the self-renewal and tumorigenicity of glioma-initiating cells, and indicate that manipulating beta1,4GalT V expression may have therapeutic potential for the treatment of malignant glioma.
    Biochemical and Biophysical Research Communications 06/2010; 396(3):602-7. · 2.48 Impact Factor
  • Article: [Stresses in portal venous system of pre-hepatic portal hypertension (PHT) rabbits].
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    ABSTRACT: Portal hypertension is a common physiopathological change in liver cirrhosis. In this study, rabbits were used and the model of pre-hepatic portal hypertension (PHT) was induced by partial ligation of portal vein in two steps. We measured the diameters of portal vein and small mesenteric vein at different time-points. Then we detected the stress forces induced by blood flow in varicose veins and in portal vein; such forces included hydrostatic pressure, shear stress and circumferential stress. With the increase of the diameter of varicose small mesenteric vein, the hydrostatic pressure and circumferential stress gradually elevated and shear stress descended markedly in both the portal vein and the small mesenteric vein of PHT rabbits, between which there was a positive linear correlation. The findings in our study indicate that the complications of PHT are partially attributable to the environment of lower shear stress and higher circumferential stress in which the blood vessels of portal venous system live.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 01/2009; 25(6):1322-6.
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    Article: E-cadherin decreased human breast cancer cells sensitivity to staurosporine by up-regulating Bcl-2 expression.
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    ABSTRACT: E-cadherin, a well-characterized cell-cell adhesion molecule, executes multifunction roles on cell behaviors. However, its effect on chemo-resistance remains controversial. In this study, we found that E-cadherin positive breast cell lines were less sensitive to staurosporine compared to E-cadherin negative ones. Next, we substantiated that the expression of E-cadherin in MDA-MB-435 cells could partly counteract the cytotoxic effect induced by staurosporine through a series of apoptosis assay. The resistance of E-cadherin over-expressing cells to staurosporine may due to the up-regulation of Bcl-2/Bax ratio. When E-cadherin interference plasmids were transfected into MCF-7 cells, Bcl-2 expression was down-regulated. Moreover, perturbation of E-cadherin function by blocking the cell-cell contact resulted in decreased cellular levels of Bcl-2 protein expression. All these results demonstrated the chemo-resistance function of E-cadherin in the condition of staurosporine treatment, therefore, might contribute effective therapeutic strategies in breast carcinoma.
    Archives of Biochemistry and Biophysics 12/2008; 481(1):116-22. · 2.93 Impact Factor
  • Article: Increase in beta1-6 GlcNAc branching caused by N-acetylglucosaminyltransferase V directs integrin beta1 stability in human hepatocellular carcinoma cell line SMMC-7721.
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    ABSTRACT: In this study, an enzymatic inactive mutant of GnT-V (delta cGnT-V) was constructed and transfected in SMMC 7721 cell line. Integrin beta1 in delta cGnT-V transfectants (delta c-7721) showed attenuation of the number of beta1-6 GlcNAc branching, whereas those in wtGnT-V transfectants (wt-7721) presented a beta1-6 GlcNAc-rich pattern. High integrin beta1 expression was observed in wt-7721 compared with mock cells (7721 cell transfected with the vector pcDNA3), while transfection of delta cGnT-V decreased the integrin beta1 expression, despite of no significant changes on integrin beta1 mRNA level in these cell lines. Pulse-chase experiment showed that Integrin beta1 in delta c-7721 was prone to quick degradation and its half-life was less than 3 h, on the contrary, the alleviating degradation of beta1 subunit was observed in wt-7721 where the beta1 subunit half-life was about 16 h, meanwhile, the degradation rate of beta1 subunit in mock cells was in between, about 10 h. More effective in promoting cell migration toward fibronectin and invasion through Matrigel was observed in wt-7721 while this was almost suppressed in delta c-7721. Our results suggest that the addition of beta1-6 GlcNAc branching caused more fully glycosylated mature form on integrin beta1 and inhibited beta1 protein degradation. Glycosylation caused by GnT-V directs integrin beta1 stability and more delivery to plasma membrane, subsequently promotes Fn-based cell migration and invasion.
    Journal of Cellular Biochemistry 02/2007; 100(1):230-41. · 2.87 Impact Factor
  • Article: [Change of zero-stress state of portal vein in the rat during the pathogenesis of intrahepatic portal hypertension].
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    ABSTRACT: A model of intrahepatic portal hypertension was established in SD rats by injection of carbon tetrachloride (CCl4). By observing the opening angle of the portal vein, the zero-stress state of the portal veins was studied at different time during the pathogenesis of intrahepatic portal hypertension. After CCl4 injection, the opening angles of the portal veins were increased, in the tenth week, they were much greater than those in the corresponding controls (P<0.05). The results suggest that during the pathogenesis of portal hypertension, unequal remodeling exists in the portal veins to change its biomechanical properties, and the residual stress and strain of the portal veins in portal hypertensive rats are greater than those in normal controls.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 09/2006; 23(4):753-5.
  • Article: Approximate entropy of fetal heart rate variability as a predictor of fetal distress in women at term pregnancy.
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    ABSTRACT: The aim of this study is to investigate the relationship between approximate entropy (ApEn) of fetal heart rate (FHR) with umbilical blood gas parameters and the power spectrum of FHR variability in Chinese and to test whether ApEn of FHR variability could be used as a predictor of fetal distress in women at term pregnancy. Sixty-seven pregnant women with singleton, term fetus were recruited for the recording of FHR variability and the data were used for the estimate of ApEn. Blood gases after birth were measured through umbilical artery. In all 67 neonates, there was some amount of interinfant variability in the ApEn values with a mean of 1.139 +/- 0.169. The ApEn values were significantly (P < 0.05) correlated with pO(2), SO(2), pCO(2), pH, HCO(3), or base excess (BE). The 15 fetuses with low ApEn (ApEn <1.0) had higher risk of metabolic acidosis (BE less than -12 mmol/l) than those with high ApEn (ApEn > or =1) (likelihood ratio = 12.301, P < 0.001). The powers of FHR variability in all frequency ranges (0-0.256 Hz) were lower in the low-ApEn group than those in the high-ApEn group. The ApEn of FHR variability significantly decreased during fetal asphyxia, including hypoxia, hypercapnia, and both respiratory and metabolic acidosis; low ApEn was linked to decreased power spectrum density in all frequency domains. The ApEn values may be used as a predictor of fetal distress in women at term pregnancy.
    Acta Obstetricia Et Gynecologica Scandinavica 09/2005; 84(9):837-43. · 1.77 Impact Factor
  • Article: [Pulse pressure and mean pressure relationship of intracranial pressure and lumbar cerebrospinal fluid pressure].
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    ABSTRACT: Intracranial pressure fluctuates due to heart beat, respiration, neuro-regulation, etc. Traditional intracranial pressure study focuses on the static pressure and related factors, putting emphasis on mean intracranial pressure, while paying little attention to the pulse components. This study was composed of two parts: animal experiment and theoretical analysis. The animal experiment was performed on 14 mongrel dogs, studying the variation of intracranial pressure wave form under different intracranial pressure level. The dogs were installed epidurally with latex sacculus to establish models of increased intracranial pressure. The degree of intracranial pressure and volume could be altered by changing the volume of fluid in the sacculus. During the process, pressure transducers were arranged to monitor and record the variations of the pressure of intracranial ventricle and lumbar subarachnoid cavity. The result demonstrated that, with the continual increase of intracranial pressure, intracranial pulse pressure increased correspondingly, showing a linear relationship with the change of intracranial pressure. After the sacculus was emptied and reinfused, the slope of the linear relationship was determined to be greater than the former slope. The same result was obtained in the lumbar cerebrospinal fluid pressure. Therefore, the lumbar cerebrospinal fluid pressure is consistent with the intracranial pressure. Intracranial pulse pressure is in linear relationship with mean pressure, and the slope of their linear relationship predicts the perform of intracranial autoregulation.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 09/2005; 22(4):704-7.
  • Article: [Approximate entropy analysis of fetal heart rate variability and its application in the diagnosis of fetal distress].
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    ABSTRACT: To introduce approximate entropy (ApEn) in the analysis of fetal heart rate variability (FHRV) and to discuss the relationship between the ApEn values and perinatal outcomes, 67 computerized cardiotocographs were recorded. Approximate entropy and index in time domain were used to analyze FHRV. After childbirth, the neonatal Apgar scores were recorded and umbilical cord arterial blood gas analyses were performed. The results showed the ApEn values of FHRV were correlated with pH, Pco2, Po2, HCO3-, ABE, SO2 and neonatal Apgar scores (r = 0.51, -0.29, 0.49, 0.29, 0.45, 0.56, 0.28, respectively, P < 0.05). The ApEn values for acidotic fetuses (pH less than 7.20) were significantly different from those of normal fetuses (P < 0.01), however the time domain parameters of FHRV were unable to identify the difference. The results suggest that the ApEn values of FHRV are closely related to the fetal hypoxia and acidemia. Thus the ApEn analysis appears to be useful for improving the sensitivity in the diagnosis of fetal distress.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 07/2005; 22(3):490-3.
  • Article: [Power spectral analysis on heart rate variability of hypoxaemia in fetal lambs].
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    ABSTRACT: To analyze the effect of hypoxaemia on heart rate variability (HRV) in fetal lambs by means of power spectrum, the intrauterine surgical operations were performed at 116-125 gestational days in 7 lambs. Arterial catheter was inserted in the fetal femoral artery and sent to aorta abdominalis, and blood pressure was recorded continually on tape recorder. The microspheres were injected via the arterial catheter to block the micrangium of placenta, thus making an animal model of fetal hypoxaemia. The fetal blood sample was drawn through the catheter for blood gas analysis. In terms of the heart beat variability power spectral density, there were four consistent components, namely very low (VL, 0.01-0.025 cycle/beat), low (L, 0.025-0.125 cycle/beat), middle (M, 0.125-0.2 cycle/beat), and high (H, 0.2-0.5 cycle/beat). Integrated peaks in the power spectrum were compared before and after administration of microsphere. The spectral power in the L frequency components was significantly increased (0.07 +/- 0.01 vs. 0.21 +/- 0.03, P<0.01), and the spectral power in the H frequency components was significantly reduced (0.53 +/- 0.1 vs. 0.27 +/- 0.05, P<0.05). There was no significant difference in M and VL. The times of microsphere injection were related to fetal blood pH (r=0.585, p<0.01), PCO2 (r=0.5, p<0.05) and PO2 (r=0.75, P<0.01). The results clearly demonstrate the association between change of power spectrum of heart rate variability and the effect of hypoxia of the fetus in labour.
    Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi 09/2004; 21(4):645-9.
  • Article: Redistribution of power spectrum of heart rate variability during acute umbilical artery embolism and hypoxemia in late-gestation fetal sheep.
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    ABSTRACT: Fetal heart rate variability (HRV) is subject to a number of factors, including fetal distress. The aim of this study was to investigate the power spectral distribution of fetal heart rate variability during acute hypoxemia following umbilical artery embolism and to test the hypothesis that the relative proportion of frequency domains in total power of HRV, reflects the changes in HRV during hypoxemia more closely than the absolute values. Acute hypoxemia was induced in seven catheterized late-gestation fetal sheep by repeated injections of microspheres to cause umbilical artery embolism. The very-low, low-, middle- and high-frequency domains (0-0.025, 0.025-0.125, 0.125-0.20, and 0.20-0.50 cycles/beat, respectively) were determined by power spectral analysis. Umbilical artery embolism induced marked fetal hypoxemia, hypercapnia and acidosis, accompanied by an increase in heart rate and a decrease in arterial blood pressure. These changes were associated with the increase in power over the entire frequency range and in the relative power in the low-frequency range (P<0.01), and with decrease in the relative power in the high-frequency range (P<0.05). Correlations were found between the relative power in the low- and high-frequency ranges and PO2 and between the relative power in these ranges and mean arterial blood pressure (P<0.05), but not PCO2 or pH. The present study indicates that acute hypoxemia induced by umbilical artery embolism leads to the redistribution of power spectral density of fetal HRV and that the relative proportion of individual frequency domains may reflect the changes in HRV during acute hypoxemia more closely than the absolute power values.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 07/2004; 114(2):137-43. · 1.97 Impact Factor
  • Conference Proceeding: Spectral analysis of heart rate variability and RVLM neuronaldischarge in rats
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    ABSTRACT: Spectral analysis was used to study the coherence between the blood pressure (BP) and neuronal discharge (ND), and between the heart rate variability (HRV) and neuronal discharge variability (NDV) in the rostral ventrolateral medulla (RVLM) in rats. The discharges of 28 neurons in the RVLM were recorded. The results revealed that: (1) there is an obvious coherence (k<sup>2</sup>=0.82±0.18) between ND and BP on spectrum. These neurons were classified as cardiac-related (n=18) if the coherence value was k<sup>2</sup>&ges;0.80; (2) there is also an evident coherence (k<sup>2</sup>=0.78±0.13) between NDV and high frequency (HF) component of HRV. These neurons might be HRV-related (n=14) if the coherence value was k<sup>2</sup>&ges;0.80. It indicates the integration of cardiac cycle and respiratory rhythm in the RVLM that might be important in cardiorespiratory homeostasis
    Engineering in Medicine and Biology Society, 1998. Proceedings of the 20th Annual International Conference of the IEEE;