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The involvement of signaling activation of protein kinase C in gadolinium chloride-induced cell survival and cell cycle progression in NIH3T3 cells

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Journal of Chinese Pharmaceutical Sciences 2014年第11期23卷 772-777页

作者：冯敏李金霞马孝杰范云周吴竞轩曾群杨晓改北京大学药学院化学生物学系北京100191

In the present study, we investigated the activation of protein kinase C （PKC） family in mouse embryonic fibroblast NIH3T3 cells using gadolinium chloride as a representative lanthanide ion. With live cell imaging system and confocal laser scanning microscopy, we found that the treatment of 50 μM GdCI3 promoted cell survival under the condition of serum-starvation. Moreover, better cell attachment and cytoskeleton reorganization were also observed. Additionally, GdC13 treatment resulted in the phosphorylation of PKC family at different time points. Furthermore, bisindolylmaleimide （a PKCpan inhibitor） could efficiently reduce the level of phosphorylated PKCpan （βIISer660）, alleviating ERK activation induced by GdC13. This finding indicated that the PKC activation was involved in GdC13-induced MAPK/ERK signaling and thus might contribute to GdClβ-indueed cell cycle progression and cell survival.

关键词： gadolinium chloride Cell cycle Protein kinase C Cytoskeleton ERK NIH3T3 cells

gadolinium induced apoptosis of human embryo liver L02 cell line by ROS-mediated AIF pathway

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Journal of Rare Earths 2011年第2期29卷 178-184页

作者：叶丽华施喆刘会雪杨晓达王夔 State Key Laboratories of Natural and Biomimetic Drugs at Peking University Department of Chemical Biology School of Pharmaceutical SciencesPeking University Health Science Center

Gd3＋ complexes have a variety of medical *** order to shed light on the mechanism of hepatotoxicity of Gd3＋ compounds,we investigated the effects of GdCl3 on human embryo liver cell strand （L02 cells）.The experimental results showed that long-time exposure to GdCl3 resulted in L02 cell *** incubation of L02 cells with GdCl3 first induced increase in cellular reactive oxygen species （ROS） and decrease in mitochondrial inner membrane potential （？ψm）.It later resulted in the activation of poly （ADP-ribose） polymerase （PARP） and the release of mitochondrial apoptosis-inducing factor （AIF）.The activation of caspase 3,however,was not *** could significantly reduce GdCl3-induced decrease of Δψm,release of AIF,and cell *** GdCl3 caused a significant increase in cell membrane permeability in L02,the change of cell membrane permeability was unlikely to be involved in GdCl3-induced cell ***,our experimental results suggested that GdCl3 induced apoptosis of human embryo liver L02 cell line by ROS-mediated AIF pathway.

关键词： gadolinium chloride mitochondria ROS rare earths

Role of Kupffer cells in acute hemorrhagic necrotizing pancreatitis-associated lung injury of rats

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World Journal of Gastroenterology 2006年第3期12卷 403-407页

作者： Hong-Bin Liu Nai-Qiang Cui Dong-Hua Li Chang Chen Department of Pharmacology Tianjin Institute of Acute Abdominal Diseases Tianjin 300100China Second Department of Surgery Tianjin Institute of Acute Abdominal Diseases Tianjin 300100China

AIM： To investigate the role of Kupffer cells （KCs） in acute hemorrhagic necrotizing pancreatitis-associated lung injury （AHNP-U）. METHODS： Forty-two rats were allocated to four groups [sham operation, AHNP model, gadolinium chloride （GdCl3） pretreatment, GdCl3 control]. In GdCl3 pretreatment group, GdCl3 was administered by caudal vein injection 24 h before the AHNP model induction. Blood from the iliac artery, alveolar macrophages and tissues from the pancreas and lung, were collected in six animals per group 3 and 6 h after acute pancreatitis induction. TNF-α, IL-1 of Lserum, myeloperoxidase （MPO） of lung tissue, NF-κB activation of alveolar macrophages were detected. Serum AST and ALT in sham operation group and GdCl3 control group were tested. In addition, histopathological changes of the pancreas and lung were observed under light microscope. RESULTS： MPO of lung tissue and TNF-α, IL-1 levels of serum were all reduced significantly in GdCl3 pretreatment group compared to those in AHNP group （P〈0.01）. NF-KB activation of alveolar macrophages was also attenuated significantly in GdCl3 pretreatment group compared to that in AHNP group （P〈0.01）. The pathological injury of the lung was ameliorated obviously in GdCl3 pretreatment group compared to that in AHNP group. Nevertheless, the serum amylase level did not reduce and injury of the pancreas was not prevented in GdCl3 pretreatment group. CONCLUSION： Pulmonary injury induced by AHNP is mediated by KC activation and AHNP-LI can be significantly ameliorated by pretreatment with GdCh and KCs play a vital role in AHNP-LI.

关键词： Pancreatitis-associated lung injury Kupffer cell NF-κB gadolinium chloride

gadolinium-promoted angiogenesis involves the activation of PKCα/β_2 and MAPKs in human umbilical vein endothelial cells

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Journal of Chinese Pharmaceutical Sciences 2013年第1期22卷 71-76页

作者：万箫苟宝迪王夔北京大学医学部药学院化学生物学系北京100191

gadolinium has been widely used as a contrast agent for magnetic resonance imaging in clinical practice. Recently, it was reported that gadolinium is involved in nephrogenic systemic fibrosis, although the exact mechanism by which gadolinium triggers nephrogenic systemic fibrosis remains unclear. In this study, we show that gadolinium chloride （GdC13） induced human umbilical vein endothelial cells （HUVECs） to migrate in Matrigel and tubulogenesis during wound healing. Chick chorioallantoic membrane assay confirmed that GdC13 stimulates angiogenesis. Under the optimal angiogenic concentration of GdC13 （1 0 ~tM）, intracellular calcium concentration and reactive oxygen species generation were elevated. Moreover, western blotting results indicate that in cells treated with GdC13, Ca2＋-dependent PKCa/132 was phosphorylated, and MAPKs pathways were also activated. Taken together, GdC13 has a potential effect on angiogenesis in HUVECs, and the possible mechanisms may involve oxidative stress and calcium-related signalin~ pathways.

关键词： gadolinium chloride Angiogenesis Reactive oxygen species Signaling pathways Human umbilical vein endothelial cells

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水溶性树型大分子磁共振成像造影剂的研究

水溶性树型大分子磁共振成像造影剂的研究