Xue Leng

Government of the People's Republic of China, Peping, Beijing, China

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Publications (11)27.08 Total impact

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    ABSTRACT: Although Zinc depletion induces apoptosis in different cells and tissues, exact mechanism of this action of zinc depletion is not completely understood. In our previous study, the results suggested that the significant down-regulation of MEK/ERK signaling pathway was observed in zinc deficiency neurons. Here, we investigate whether, in hippocampal neurons, this increased rate of apoptosis induced by zinc depletion is the result of hypophosphorylation of ERK pathway. In this study, we found that NGF, ERK agonist, prevented neurons against TPEN-induced apoptosis, whereas TPEN-induced apoptosis was potentiated by U0126, inhibitors of ERK. Moreover, TPEN-induced caspase-3 activity was further increased by the pretreatment with U0126, but it was further decreased by the pretreatment with NGF. However, pretreatment of the cells with U0126 or NGF had no effect on the changes of Bcl-2 and Bax protein expression induced by zinc depletion. Thus, the results indicate that TPEN induces apoptosis of hippocampal neurons through inhibition of ERK and, in turn, activation of caspase-3.
    Neuroscience Letters 08/2013; 552. DOI:10.1016/j.neulet.2013.07.057 · 2.03 Impact Factor
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    ABSTRACT: Although previous studies have shown that autoantigens such as Hsps have been implicated by induction of an autoimmune process in the development of atherosclerosis, the exact role of anti-Hsp70 antibody in atherosclerosis is unknown. In the present study, the levels of anti-Hsp70 autoantibodies and oxidized low density lipoprotein (OxLDL) were all significantly increased, and they were strongly correlated in an atherosclerosis model. After the endothelial cells were incubated with 20 μg/mL OxLDL for 12 h at 37 °C and followed by 90 min recovery, Hsp70 positive staining of OxLDL-treated endothelial cells was observed on the cell surface in immunostaining and flow cytometric analysis. This membrane Hsp70 was not from culture supernatant Hsp70 and binding of extracellular Hsp70 but was defined as endothelial surface membrane Hsp70. Furthermore, only in the OxLDL-treated group, but not in the untreated group, (51)Cr-labeled endothelial cells were lysed by anti-Hsp70 antibody (BD091, Ig(AS)) in the presence of either complement or peripheral blood mononuclear cells. Control antibodies, including Ig(Nor), mAb to Hsp70 (SPA-810), and mAbs to Factor VIII, α-actin, and CD3 showed no cytotoxic effects. In conclusion, anti-Hsp70 antibodies could be reacting with the endothelial surface membrane Hsp70 induced by OxLDL and were able to mediate endothelial cytotoxicity. There is a possibility that a humoral immune reaction to endothelial surface membrane Hsp70 may play an important role in the pathogenesis of atherosclerosis.
    Cell Stress and Chaperones 01/2013; 18(4). DOI:10.1007/s12192-013-0404-4 · 3.16 Impact Factor
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    ABSTRACT: To investigate the dynamic expression of Heat shock protein 70 (Hsp70) in the lungs and plasma of rats with pulmonary fibrosis induced by silicon dioxide (SiO2). Forty-eight Wistar rats were randomly divided into the control group exposed to normal solution and group exposed to SiO2 (50 mg/ml) with intratracheal injection. Each group was divided into four subgroups. The animals of SiO2 group and control group were sacrificed and lungs were collected on the 7th, 14th and 28th days after exposure, respectively. The left lung tissues were examined with the histopathologic HE staining. The expression and localization of Hsp70 protein in the lung tissues were examined with western blot assay and immunohistochemistry, respectively. The expression levels of Hsp70 protein in the plasma were measured by ELISA. The expression of Hsp70 in lung tissues of SiO2 group increased on the 7th day and reached the peak value on the 14th day then decreased, but still was significantly higher than that of the control group, the expression of Hsp70 in plasma of SiO2 group still was significantly higher than that of the control group (P < 0.05). The maximum expression level of Hsp70 in plasma of SiO2 group on the 21st day after exposure was 0.216 ± 0.027 µg/ml. The expression levels of Hsp70 protein in the lung tissues and plasma of the group exposed to SiO2 significantly increased, which were associated with the process of pulmonary fibrosis. It was suggested that Hsp70 protein may play an important biological role in the pulmonary fibrosis induced by SiO2.
    Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases 06/2012; 30(6):428-31.
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    ABSTRACT: An experiment was performed to observe the changes in Raf-1 kinase/mitogen-activated protein kinase ERK (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in cultured hippocampal neurons and its correlation with neurons apoptosis induced by intracellular zinc depletion. Cultured hippocampal neurons were exposed to a cell membrane-permeant zinc chelator TPEN (2 µM), and to TPEN plus zinc sulfate (5 µM) for 24 h. Cultures were then processed to detect neuronal viability by the methyl thiazolyl tetrazolium assay, while apoptosis rate was simultaneously observed by the flow cytometric analysis. Caspase-3, Raf-1, pMEK, pERK1/2, and pCREB protein levels were examined by Western blot assays. The viability in TPEN-incubated neurons was notably decreased, apoptosis rate and expression of caspase-3 significantly increased compared to untreated controls. The significant down-regulation of Raf/MEK/ERK signaling pathway and expression of pCREB were decreased in TPEN-treated neurons. Co-addition of zinc almost completely reversed TPEN-induced alterations described. The results demonstrated zinc-modulated apoptosis and the expression of Raf/MEK/ERK at the protein level in hippocampal neurons. It is possible that zinc depletion-induced apoptosis in cultured hippocampal neurons may be relevant to the changes of Raf/MEK/ERK signaling pathway.
    Nutritional Neuroscience 01/2012; 15(1):18-24. DOI:10.1179/1476830511Y.0000000031 · 2.27 Impact Factor
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    ABSTRACT: It has been previously reported that the plasma levels of autoantibodies against heat shock protein 70 (HSP70) are elevated in atherosclerosis. The aim of the present study was to elucidate whether anti-HSP70 antibodies are involved in the pathogenesis of atherosclerosis. To determine this, we chose rats as an atherosclerosis model. Titers of plasma anti-HSP70 autoantibody were determined by ELISA. After the intravenous administration of antibody into the tail, the damaged areas of aorta were stained with Evans Blue, atheromatous plaque were stained by Oil Red O, and then they were measured and quantified with AxioVision computer software. The number of macrophages ([Formula: see text]), smooth muscle cells (SMCs), and T cells were determined by immunocytochemistry. The level of anti-HSP70 IgG1 antibody was apparently increased in the AS group at the tenth week, and one hybridoma of HSP70 antibody (BD091, IgG1, recognizing C-terminal) had the same binding epitope as plasma anti-HSP70 autoantibodies. After intravenous administration, the lesion area of aorta with BD091 was significantly larger than those of IgG(mouse) and SPA-810. Moreover, injection of BD091 resulted in significant endothelium damage, followed by a greater accumulation of [Formula: see text], T cells, and SMCs in lesions than in the control. In conclusion, BD091 reaction with HSP70 expressed on arterial endothelial cells inducing endothelium damage triggers the inflammatory response in the vessel wall that accelerates atherosclerosis in rats. BD091 shares the same binding epitope with HSP70 autoantibodies. These data indicated that a specific epitope of anti-HSP70 autoantibody participated in the pathogenesis of atherosclerosis.
    Cell Stress and Chaperones 11/2010; 15(6):947-58. DOI:10.1007/s12192-010-0203-0 · 3.16 Impact Factor
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    ABSTRACT: It has been confirmed that stress plays an important role in the induction and development of cardiovascular diseases, but its mechanism and molecular basis remain unknown. In the present study, a myocardial injury model induced by restraint stress was established in rat. To screen for the related proteins involved in stress-induced myocardial injury, proteomic techniques based on 2-DE and mass spectrometry were used. In our results, ten proteins were found to be altered. The expression of eight of these proteins was increased after restraint stress, including cardiac myosin heavy chain, dihydrolipoamide succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial aldehyde dehydrogenase, H(+)-transporting ATP synthase, albumin, and apolipoprotein A-I precursor. The expression of uncoupling protein 3 (UCP3) and mitochondrial aconitase was decreased. Most of the proteins were related to energy metabolism. Further research indicated that UCP3 may mediate the myocardial cell response induced by restraint stress.
    Cell Stress and Chaperones 04/2010; 15(6):771-9. DOI:10.1007/s12192-010-0185-y · 3.16 Impact Factor
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    ABSTRACT: To explore the level of anti-HSP70 antibody in plasma during atherosclerosis procedure induced by high-fat diet in rat and the relationship of them. Twenty eight rat were divided into high-fat diet group (H) and control group (C). The total cholesterol (TC), Glyceride (TG), low density lipoprotein cholesterol (LDL-C) in serum, pathology change of rat Arch of the aorta were determined, the level of anti-HSP70 antibody and their Phenotype were evaluated by ELISA. After two weeks, the serum concentrations of TC and LDL-C in rat supplemented by high-fat diet were significantly higher than those in control group (P < 0.01), the serum TG were much lower than those in control group (P < 0.01). Four weeks later the level of anti-HSP70 antibody, IgM, IgG phenotype were significantly higher than those in control group (P < 0.01). There were lipin deposition and mottling formation in rat Arch of the aorta in rat supplemented by high-fat diet in 12th week. Atherosclerosis could be induced by high-fat diet in rat. Accompany with the atherosclerosis procession, the level of anti-HSP70 antibody was continuously elevated, the level of anti-HSP70 antibody was related to atherosclerosis. The level of anti-HSP70 antibody was closely associated with atherosclerosis.
    Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 11/2009; 25(4):450-4.
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    ABSTRACT: Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity.
    Biochemical and Biophysical Research Communications 09/2009; 387(2-387):229-233. DOI:10.1016/j.bbrc.2009.06.095 · 2.30 Impact Factor
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    ABSTRACT: NGFI-B/Nur77/TR3, originally identified as an immediate-early gene rapidly induced by serum and growth factors, is a member of the steroid hormone nuclear receptor superfamily with no identified endogenous ligand. NGFI-B induces apoptosis in a number of cell lineages exposed to proapoptotic stimuli by directly targeting the mitochondria, inducing cytochrome c release. The present study was designed to determine the role of NGFI-B in cardiomyocytes of restraint-stressed rats. The NGFI-B content was increased in mitochondria and reduced in plasma as apoptosis increased. Analysis showed that NGFI-B induces cardiomyocyte apoptosis in restraint-stressed rats by mediating mitochondrial energy metabolism disorder. Several novel mitochondrial proteins, which correlate with NGFI-B, were reported in cardiomyocyte apoptosis of restraint-stressed rats. Five proteins associated with NGFI-B participate directly in mitochondrial energy metabolism. Studies of mitochondrial respiratory efficiency and ATP synthase activity strongly support the findings. These results provide significant information for comprehensively understanding the cellular mechanism of cardiovascular diseases.
    Cell Stress and Chaperones 06/2009; 14(6):639-48. DOI:10.1007/s12192-009-0116-y · 3.16 Impact Factor
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    ABSTRACT: Oxidative stress is one of the main causes of myocardial injury, which is associated with cardiomyocyte death. Mitochondria play a key role in triggering the necrosis and apoptosis pathway of cardiomyocytes under oxidative stress. Although prohibitin (PHB) has been acknowledged as a mitochondrial chaperone, its functions in cardiomyocytes are poorly characterized. The present research was designed to investigate the cardioprotective role of PHB in mitochondria. Oxidative stress can increase the PHB content in mitochondria in a time-dependent manner. Overexpression of PHB in cultured cardiomyocytes by transfection of recombinant adenovirus vector containing PHB sense cDNA resulted in an increase of PHB in mitochondria. Compared with the non-transfection cardiomyocytes, PHB overexpression could protect the mitochondria from oxidative stress-induced injury. The mitochondria-mediated apoptosis pathway was consistently suppressed in PHB-overexpressed cardiomyocytes after hydrogen peroxide (H(2)O(2)) treatment, including a reduced change in mitochondrial membrane permeability transition and an inhibited release of cytochrome c from mitochondria to cytoplasma. As a result, the oxidative stress-induced cardiomyocyte apoptosis was suppressed. These data indicated that PHB protected the cardiomyocytes from oxidative stress-induced damage, and that increasing PHB content in mitochondria constituted a new therapeutic target for myocardium injury.
    Cell Stress and Chaperones 11/2008; 14(3):311-9. DOI:10.1007/s12192-008-0086-5 · 3.16 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia is a common independent risk factor for cardiovascular diseases. The promoting effect of homocysteine (Hcy) on vascular smooth muscle cell (VSMC) proliferation has been considered as one of the important pathological bases of atherosclerosis. However, the mechanism of VSMC proliferation induced by Hcy remains unclear. The present research used proteomic techniques to globally analyze the protein changes in proliferative VSMCs. After comparing the protein expression profiles of VSMCs between the Hcy-treated and non-treated groups, 11 protein spots were found altered markedly in proliferative VSMCs with expression of eight protein spots increased and three protein spots decreased. In the differentially expressed proteins, eight protein spots were identified successfully including glycolytic metabolism proteins: pyruvate kinase M2 (PKM2), triosephosphate isomerase (TPI) and aldose reductase (AR); cytoskeletal proteins: lamin C and vimentin; and three other proteins: calreticulin; similar to WDR1 protein and LIM and SH3 protein 1. The differentially expressed proteins were further validated by Western blot and confirmed by assay of enzymes' activities and ATP content. These results may provide some clues for comprehensively understanding the mechanism of VSMC proliferation and pathogenesis of atherosclerosis induced by Hcy.
    Biochimica et Biophysica Acta 11/2008; 1794(2):177-84. DOI:10.1016/j.bbapap.2008.10.001 · 4.66 Impact Factor

Publication Stats

116 Citations
27.08 Total Impact Points


  • 2013
    • Government of the People's Republic of China
      Peping, Beijing, China
  • 2009–2013
    • Academy of Military Medical Sciences
      T’ien-ching-shih, Tianjin Shi, China
  • 2012
    • Hebei University
      Pao-ting-shih, Hebei, China
  • 2008–2010
    • Tianjin Institute of Health And Environmental Medicine
      T’ien-ching-shih, Tianjin Shi, China