Bio pharmaceutical Key Laboratory of Heilongjiang Province

Harbin, China

Bio pharmaceutical Key Laboratory of Heilongjiang Province

Harbin, China
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Li C.,Harbin Medical University | Jiang Z.,Fudan University | Liu X.,Bio pharmaceutical Key Laboratory of Heilongjiang Province
Biological Trace Element Research | Year: 2010

The possible biochemical mechanism of gallium was studied in this paper. One-day-old hens were fed to up to 68 weeks on a control diet and diets containing gallium. Serum calcium and phosphorus, serum alkaline phosphatase, tartrate resistant acid phosphatase (TRAP), serum osteocalcin, homocysteine, C-terminal crosslinked telopeptides of collagen type I, and bone mineral content were measured, respectively. The beneficial effects of gallium supplementation on improvement of cage layer osteoporosis were attributable mainly to decrease TRAP activity, C-terminal crosslinked telopeptides of collagen type I level, plasma calcium and phosphate concentrations, and increase the mineral content in the bones and osteocalcin level in plasma. © 2009 Humana Press Inc.


Liu H.-B.,Harbin Medical University | Yang B.-F.,Harbin Medical University | Dong D.-L.,Harbin Medical University | Dong D.-L.,Bio pharmaceutical Key Laboratory of Heilongjiang Province
Trends in Cardiovascular Medicine | Year: 2010

Calcineurin is a cytoplasmic Ca 2+/calmodulin-dependent protein phosphatase that contributes to cardiac hypertrophy. Numerous studies have demonstrated that calcineurin/nuclear factor of activated T cell pathway affects the architecture of the heart under pathologic conditions, and the effects of calcineurin/nuclear factor of activated T cell pathway on cardiac hypertrophy have been well reviewed. Cardiac electrical remodeling is generally accompanied with the cardiac hypertrophy, and alteration of cardiac ion channel activity also leads to the changes of calcineurin activity and cardiac hypertrophy. Many studies have linked calcineurin with changes of a variety of ion channels, but the therapeutic approaches to target calcineurin for correcting cardiac electrical disturbance have not been formulated. Here, we review the recent progress in calcineurin and electrical remodeling in pathologic cardiac hypertrophy. © 2010 Elsevier Inc.


Liu Y.,Harbin Medical University | Ma C.,Harbin Medical University | Zhang Q.,Harbin Medical University | Yu L.,Harbin Medical University | And 7 more authors.
International Journal of Biochemistry and Cell Biology | Year: 2012

Our laboratory has proved that 15-hydroxyeicosatetraenoic acid, a product of arachidonic acid catalyzed by 15-lipoxygenase (15-LO), plays a pivotal role in hypoxic pulmonary arterial hypertension. However, the mechanisms of how hypoxia regulates 15-LO expression are still unclear. As the formation of endogenous transforming growth factor-beta1 (TGF-β1), implicated in pulmonary arterial hypertension pathogenesis, was promoted by hypoxia, we suspect whether hypoxia-induced the expression of 15-LO is via the TGF-β1 pathway. We found that treatment of pulmonary artery smooth muscle cells with TGF-β1 significantly increased the expression of 15-LO and levels of 15-hydroxyeicosatetraenoic acid, product of 15-LO, which were inhibited by transforming growth factor-beta receptor I (TGFβRI) inhibitor, SD-208 and siRNA targeted to knockdown rat TGFβRI. Moreover, our results showed that TGF-β1 regulated the cell cycle progression and made more cells from the G0/G1 phase to the G2/M + S phase and enhanced the microtubule formation in cell nucleus. Additionally, we found that the 15-LO pathway was involved in TGFβ-1-mediated cell viability, DNA synthesis and the cell cycle progression. Our data provide novel evidence that hypoxia induced 15-LO expression is through TGF-β1, and 15-LO pathway plays a critical role in TGFβRI mediated the proliferation of pulmonary artery smooth muscle cells induced by hypoxia. Thus, new strategies aimed at combined blockade of TGFβRI as well as 15-LO may yield optimal therapeutic benefits. Crown Copyright © 2012 Published by Elsevier Ltd. All rights reserved.


Liu F.,Harbin Medical University | Yu Y.,Harbin Medical University | Jin Y.,Harbin Medical University | Fu S.,Harbin Medical University | Fu S.,Bio Pharmaceutical Key Laboratory of Heilongjiang Province
Molecular Biology Reports | Year: 2010

Understanding the genesis and development of tumors is an essential component in cancer research. It is of interest to discover unknown genes that are responsible for cellular transformation. A cDNA library of a highly metastatic lung adenocarcinoma cell line was constructed. This library was introduced into the NIH3T3 mouse embryonic fibroblast cell line to screen for cDNAs that increase anchorage-independent colony formation in soft agar. The expression of TSG101 in lung cancer cell lines and specimens was confirmed using reverse transcription-polymerase chain reaction. The level of TSG101 protein in transfected A549 cells was determined by western blotting. Cell-cycle distribution was analyzed using a FACStar Plus flow cytometer. One of the candidate cDNAs that increases anchorage-independent colony formation was shown to correspond to the TSG101 cDNA sequence. Levels of TSG101 mRNA were higher in lung cancer cell lines and specimens compared to matched normal lung tissues. Ectopic expression of TSG101 in the A549 lung adenocarcinoma cell line increased the numbers of cells in S phase, suggesting an increased cell proliferation rate. These results indicate that TSG101 may induce the malignant phenotype of cells. © 2009 Springer Science+Business Media B.V.


Ma C.,Harbin Medical University | Li Y.,Harbin Medical University | Ma J.,Harbin Medical University | Liu Y.,Harbin Medical University | And 7 more authors.
Hypertension | Year: 2011

We have found that 15-hydroxyeicosatetraenoic acid (15-HETE) induced by hypoxia was an important mediator in the regulation of hypoxic pulmonary hypertension, including the pulmonary vasoconstriction and remodeling. However, the underlying mechanisms of the remodeling induced by 15-HETE are poorly understood. In this study, we performed immunohistochemistry, pulmonary artery endothelial cells migration and tube formation, pulmonary artery smooth muscle cells bromodeoxyuridine incorporation, and cell cycle analysis to determine the role of 15-HETE in hypoxia-induced pulmonary vascular remodeling. We found that hypoxia induced pulmonary vascular medial hypertrophy and intimal endothelial cells migration and angiogenesis, which were mediated by 15-HETE. Moreover, 15-HETE regulated the cell cycle progression and made more smooth muscle cells from the G0/G1 phase to the G2/M+S phase and enhanced the microtubule formation in cell nucleus. In addition, we found that the Rho-kinase pathway was involved in 15-HETE-induced endothelial cells tube formation and migration and smooth muscle cell proliferation. Together, these results show that 15-HETE mediates hypoxia-induced pulmonary vascular remodeling and stimulates angiogenesis via the Rho-kinase pathway. © 2011 American Heart Association, Inc.


Ma J.,Harbin Medical University | Liang S.,Harbin Medical University | Wang Z.,Harbin Medical University | Zhang L.,Harbin Medical University | And 7 more authors.
Journal of Cellular Physiology | Year: 2010

15-Hydroxyeicosatetraenoic acid (15-HETE), a product of arachidonic acid (AA) catalyzed by 15-lipoxygenase (15-LO), plays an essential role in hypoxic pulmonary arterial hypertension. We have previously shown that 15-HETE inhibits apoptosis in pulmonary artery smooth muscle cells (PASMCs). To test the hypothesis that such an effect is attributable to the hypoxia-induced pulmonary vascular remodeling (PVR), we performed these studies. We found subtle thickening of proximal media/adventitia of the pulmonary arteries (PA) in rats that had been exposed to hypoxia. This was associated with an up-regulation of the anti-apoptotic Bcl-2 expression and down-regulation of pro-apoptotic caspase-3 and Bax expression in PA homogenates. Nordihydroguaiaretic acid (NDGA), which inhibits the generation of endogenous 15-HETE, reversed all the alterations following hypoxia. In situ hybridization histochemistry and immunocytochemistry showed that the 15-LO-1 mRNA and protein were localized in pulmonary artery endothelial cells (PAECs), while the 15-LO-2 mRNA and protein were localized in both PAECs and PASMCs. Furthermore, the Rho-kinase (ROCK) pathway was activated by both endogenous and exogenous 15-HETE, alleviating the serum deprivation (SD)-induced PASMC apoptosis. Thus, these findings indicate that 15-HETE protects PASMC from apoptosis, contributing to pulmonary vascular medial thickening, and the effect is, at least in part, mediated via the ROCK pathway. © 2009 Wiley-Liss, Inc.


Jiang J.,Harbin Medical University | Wang S.,Harbin Medical University | Wang Z.,Harbin Medical University | Ma J.,Harbin Medical University | And 4 more authors.
Journal of Receptors and Signal Transduction | Year: 2011

15-Hydroxyeicosatetrenoic acid (15-HETE) is an important product of arachidonic acid catalyzed by 15-lipoxygenase (15-LO) in the wall of pulmonary vessels, which plays a key role in pulmonary arterial hypertension. The previous studies showed that 15-HETE inhibits apoptosis. It is still unknown, however, whether 15-HETE acts on the apoptotic responses through the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. The aim of the study is to test the hypothesis that ERK1/2 pathway participates in the protective effects of 15-HETE on the cell survival. This hypothesis was validated by cell viability measurement, nuclear morphology determination, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, mitochondrial potentials assay and Western blot. We found that 15-HETE enhanced cell survival, suppressed the expression of phosphatase and tensin homologue deleted on chromosome ten, upregulated X-linked inhibitor of apoptosis protein and Bcl-2 and attenuated mitochondrial depolarization in pulmonary artery muscle smooth cells (PASMCs) under serum-deprived conditions. These effects were reversed by ERK1/2 inhibitor PD98059. Taken together, our data indicated that the ERK1/2 kinase is a regulator of PASMC apoptosis, and potential therapeutical strategy for pulmonary hypertension may be developed by targeting at intracellular signaling systems centered by the kinase. © 2011 Informa Healthcare USA, Inc.


Ma C.,Harbin Medical University | Wang Y.,Harbin Medical University | Shen T.,Harbin Medical University | Zhang C.,Harbin Medical University | And 5 more authors.
Prostaglandins Leukotrienes and Essential Fatty Acids | Year: 2013

Our previous studies have proved that hypoxia enhances the 15-lipoxygenase (15-LO) expression and increases endogenous 15-hydroxyeicosatetraenoic acid (15-HETE) production to promote pulmonary vascular remodeling and angiogenesis, while the mechanisms of how hypoxia regulates 15-LO expression in endothelium is still unknown. As placenta growth factor (PlGF) promotes pathological angiogenesis by acting on the growth, migration and survival of endothelial cells, there may be some connections between PlGF and 15-LO in hypoxia induced endothelial cells proliferation. In this study, we performed immunohistochemistry, pulmonary artery endothelial cells migration and bromodeoxyuridine incorporation to determine the role of PlGF in pulmonary remodeling induced by hypoxia. Our results showed that hypoxia up-regulated PlGF expression, which was mediated by 15-LO/15-HETE pathway. Furthermore, we found that PlGF had a positive feedback regulation with 15-LO expression and 15-HETE generation. The interaction in hypoxia between 15-HETE and PlGF created a PlGF-15-LO-15-HETE loop, leading to endothelial dysfunction. Thus, these findings suggest a new therapeutic agent in combination with the blockade of PlGF as well as 15-LO in hypoxic pulmonary hypertension. © 2013 Elsevier Ltd.


Xu L.,Harbin Medical University | Sun H.,Harbin Medical University | Zhang X.,Harbin Medical University | Wang J.,Harbin Medical University | And 5 more authors.
Scandinavian Journal of Gastroenterology | Year: 2010

Objective. It has been reported that some single-nucleotide polymorphisms (-13910C/T, -22018G/A, -13907C/G, -13915T/G, and -14010G/C) within the lactase gene are associated with lactase persistence. In our previous study, we found that -13910C/T is not a good predictor of lactase persistence in Chinese populations. To obtain a better understanding of the mechanism of lactase persistence, we examined the frequencies in Northern China of the four other alleles that are associated with lactase persistence. Material and methods. We evaluated the allele frequencies of -22018G/A, -13907C/G, -13915T/G, and -14010G/C in six northern Chinese populations (Manchu, Mongol, Hezhen, Oroqen, Kazak, and northern Han) using the methods of polymerase chain reactionrestriction fragment length polymorphism and resequencing. Results. By genotyping 1092 chromosomes, we found that the frequency of the -22018A allele was highest in the Kazak population and extremely low in the northern Han population. Although there are little available data about the frequency of lactase persistence in northern Chinese populations, we compared the allele frequencies with the phenotype frequencies that have been published previously. We found that the frequency of the -22018A allele was basically consistent with the reported frequencies of lactase persistence in Northern China. With respect to the -13907C/G, -13915T/G, and -14010G/C polymorphisms, we found no individuals with the derived allele. Conclusions. The frequency of the -22018A allele differed significantly among the six populations and the frequency reflected the frequency of lactase persistence. Taking into consideration the results of previous studies, we believe that the origins of lactase persistence-associated alleles are different in different pastoral populations.


Ma C.,Harbin Medical University | Liu Y.,Harbin Medical University | Wang Y.,Harbin Medical University | Zhang C.,Harbin Medical University | And 7 more authors.
British Journal of Pharmacology | Year: 2014

Background and Purpose Dysfunction and injury of endothelial cells in the pulmonary artery play critical roles in the hypertension induced by chronic hypoxia. One consequence of hypoxia is increased activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). Here, we have explored, in detail, the effects of hypoxia on the proliferation of pulmonary artery endothelial cells. Experimental Approach We used bromodeoxyuridine incorporation, cell-cycle analysis, immunohistochemistry and Western blot analysis to study the effects of hypoxia, induced 15-PGDH) activity and its product, 15-keto-6Z, 8Z, 11Z, 13E-eicosatetraenoic acid (15-KETE), on endothelial cell proliferation. Scratch-wound and tube formation assays were also used to study migration of endothelial cells. Key Results 15-KETE increased DNA synthesis and enhanced the transition from the G0/G1 phase to the S phase in hypoxia. Inhibition of 15-PGDH or siRNA for 15-PGDH reversed these effects. 15-KETE also activated the ERK1/2 signalling pathway. 15-KETE-induced cell migration and tube formation were reversed by blocking ERK1/2, but not the p38 MAPK pathway. Conclusions and Implications Hypoxia-induced endothelial proliferation and migration, an important underlying mechanism contributing to hypoxic pulmonary vascular remodelling, appears to be mediated by 15-PGDH and 15-KETE, via the ERK1/2 signalling pathway. © 2014 The British Pharmacological Society.

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