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刘建辉, Jianhui Liu a, Fei Yin a, Xuxu Zheng a, Jiajia Jing a, Yinhe Hu b
Neurochemistry International 51(2007)361-369,-0001,():
-1年11月30日
Alzheimer's disease (AD) is the most common form of dementia. Glucagon-like peptide-1 (GLP-1) gives a new genre in therapeutic targets for intervention in AD with its neurotrophic and neuroprotective functions. In previous work, we identified that geniposide is a novel agonist for GLP-1 receptor, which shows neurotrophic characteristics to induce the neuronal differentiation of PC12 cells. The aim of this study is to determine whether geniposide prevents neurons from oxidative damage, and to explore its signaling pathways. The results demonstrated that geniposide increased the expression of anti-apoptotic proteins, including Bcl-2 and heme oxygenase-1 (HO-1), to antagonize the oxidative damage in PC12 cells induced by hydrogen peroxide. LY294002 (a PI3K inhibitor) inhibited the effect of geniposide increasing of Bcl-2 level by activation of MAPK, MEK and c-Raf phosphorylation in hydrogen peroxide treated PC12 cells. U0126 (a selective inhibitor of MEK) also attenuated the enhancement of geniposide on Bcl-2 level by inhibiting the phosphorylation of p90RSK in the hydrogen peroxide treated PC12 cells. All these data demonstrate that geniposide, an agonist for GLP-1 receptor, regulates expression of anti-oxidative proteins including HO-1 and Bcl-2 by activating the transcriptor of p90RSK via MAPK signaling pathway in PC12 cells.
Geniposide, Glucagon-like peptide-1 receptor, Oxidative stress, Mitogen-activated protein kinase
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【期刊论文】Neurotrophic property of geniposide for inducing the neuronal differentiation of PC12 cells
刘建辉, Jianhui Liu a, Xuxu Zheng a, Fei Yin a, Yinhe Hu b, Lixia Guo a, Xiaohong Deng a, Gang Chen a, Jing Jiajia a, b, Heng Zhang a
Int. J. Devl Neuroscience 24(2006)419-424,-0001,():
-1年11月30日
The emerging data show that the insulinotrophic hormone glucagon-like peptide-1(GLP-1) and its agonist extendin-4 have neurotrophic function to inducing neuronal differentiation of PC12 cells and prevent neurons damage challenged by oxidative stress. Here, with the model of high throughput screen for GLP-1 receptor agonists, we screen and identify that geniposide is a novel agonist for GLP-1 receptor. Furthermore, geniposide induces the neuronal differentiation of PC12 cells with resulting neurites outgrowth; we also observe an increase in expression of growth-associated protein-43. U0126, a selective MEK inhibitor, prevents neurites out growth and phosphorylation of mitogen-activated kinase proteins in PC12 cells induced by geniposide. All these results show that activation of GLP-1 receptor by geniposide to induce the neuronal differentiation of PC12 cells involves in MAPK signaling cascade.
Glucagon-like peptide-1, Geniposide, Differentiation, Neurite, Mitogen-activated protein kinase
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【期刊论文】Characterization and antitumor activity of triethylene tetramine, a novel telomerase inhibitor
刘建辉, Jianhui Liu, Lixia Guo, Fei Yin, Xuxu Zheng, Gang Chen, Yun Wang
Biomedicine & Pharmacotherapy 62(2008)480-485,-0001,():
-1年11月30日
Triethylene tetramine (TETA) is a novel ligand for G-quadruplex and has been reported to have many kinds of biological activities, including telomerase inhibition, inducing the senescence of tumor cells, etc. In this study, tumor inhibiting activity of TETA and its mechanism were investigated in HeLa cells, MCF-7 cells and mice transplanted with S180 tumor. Results indicated that TETA inhibited telomerase activity involved in decreasing the expression of human telomerase reverse transcriptase (hTERT). We also observed that a low concentration of TETA had limited ability to inhibit the growth of tumor cells in short-term culture, but it could significantly enhance antitumor activity of traditional antitumor drugs in vitro and in vivo.
Triethylene tetramine, Telomerase, Human telomerase reverse trans, c, r, i, p, t, ase (, hTERT),
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刘建辉, Shuzhen Kong, Jian-Hui Liu, Andrew G. Ramage and YunWang,
Exp Physiol 92.6 pp 1023-1028,-0001,():
-1年11月30日
Cardiac vagal preganglionic neurones (CVPNs) show respiratory modulation in the nucleus ambiguus but not in the dorsal vagal nucleus. Both types of neurones can be activated by pulmonary C fibre afferents. Another brainstem area that has been identified as containing CVPNs is the intermediate zone between the dorsal vagal nucleus and nucleus ambiguus. Experiments were carried out in α-chloralose-anaesthetized cats to determine the physiological properties of these CVPNs and their responses to pulmonary C fibre afferent activation. Seven CVPN axons in the right cardiac vagal branches were identified and found to be localized in the intermediate zone with a conduction velocity of between 1.2 and 1.6ms−1, in the C fibre range. These seven CVPNs [either showing spontaneous activity (n=1) or having activity induced by DL-homocysteic acid applied ionophoretically (n=3)] were neither respiratory modulated nor did they receive a baroreceptor input, thus being similar to those found in the dorsal vagal nucleus. Right atrial injections of phenylbiguanide excited all four CVPNs tested. In conclusion, CVPNs located in the intermediate zone have similar properties to those in the dorsal vagal nucleus but not the nucleus ambiguus.
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刘建辉, Liu Jian-Hui, Jiang Bo, Bao Yong-Ming, An Li-Jia
Int. J. Devl Neuroscience 21(2003)277-281,-0001,():
-1年11月30日
Exposure of rat pheochromocytoma PC12 cells to Cuscuta chinensis glycoside induced neuronal differentiation with resulting outgrowth of neurites and increase of acetylcholinesterase activity. A specific inhibitor of mitogen-activated protein kinase (MAPK) kinase, PD98059, prevented this effect of C. chinensis on PC12 cells. These results suggested that C. chinensis glycoside induced neuronal differentiation in PC12 cells linked to the mitogen-activated protein kinase signaling cascade.
Acetylcholinesterase, Differentiation, Cuscuta chinensis, Mitogen-activated protein kinase, Neurite
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