Tauopathies describe a group of neurodegenerative diseases in which the protein tau,encoded by the gene MAPT,is aberrantly misfolded,leading to tau aggregation,neural dysfunction,and cell death（Spillantini and Goeder...Tauopathies describe a group of neurodegenerative diseases in which the protein tau,encoded by the gene MAPT,is aberrantly misfolded,leading to tau aggregation,neural dysfunction,and cell death（Spillantini and Goedert,2013）.In Alzheimer＇s disease（AD）,tau forms the characteristic intracellular neurofibrillary tangles（NFTs）,which are thought to be the major cause of neurodegeneration（Bloom,2014）.In other tauopathies,including frontotemporal dementia with Parkinsonism linked to chromo- some 17 （FTDP-17T）, corticobasal degeneration and progressive supranuclear palsy, there are specific forms of tau aggregates and filaments without any amyloid pathology, demonstrating tau＇s po- tent disease-causing potential （Spillantini and Goedert, 2013）. Tau is a microtubule （MT） binding protein, which becomes abnormally hyperphosphorylated on several residues prior/during the process of aggregation, thereby causing loss of its MT binding activity （Mandelkow and Mandelkow, 2012）.展开更多
The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n...The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 ?3.1 kPa and 68.7 ?10.2 kPa.s / L respectively. IG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 ?4.7 kPa and 158.4 ?25 kPa.s / L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin? level in the femoral artery increased by 20.9+ 7.1, 25.6?7.7, 28.6?7.9 pg / ml at the 60 th, 120th, 180th minute after the injection of L-NAME respectively (P<0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 ?.9 pg / 105 cells /ml (n=9). L-NAME increased endothelin-1 level to 42.8 ?4.9pg / 105 cells / ml (n = 9, P < 0.05) in case of 10-11 mol / L and to 43.0+ 4.7 pg / 105 cells / ml in case of 10 -7 mol/L (n=9, F<0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin? in vivo and in cultured vascular endothelial cells.展开更多
基金funded by grant NC/L000741/1 from the National Council of the 3Rs
文摘Tauopathies describe a group of neurodegenerative diseases in which the protein tau,encoded by the gene MAPT,is aberrantly misfolded,leading to tau aggregation,neural dysfunction,and cell death（Spillantini and Goedert,2013）.In Alzheimer＇s disease（AD）,tau forms the characteristic intracellular neurofibrillary tangles（NFTs）,which are thought to be the major cause of neurodegeneration（Bloom,2014）.In other tauopathies,including frontotemporal dementia with Parkinsonism linked to chromo- some 17 （FTDP-17T）, corticobasal degeneration and progressive supranuclear palsy, there are specific forms of tau aggregates and filaments without any amyloid pathology, demonstrating tau＇s po- tent disease-causing potential （Spillantini and Goedert, 2013）. Tau is a microtubule （MT） binding protein, which becomes abnormally hyperphosphorylated on several residues prior/during the process of aggregation, thereby causing loss of its MT binding activity （Mandelkow and Mandelkow, 2012）.
文摘The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin?1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 ?3.1 kPa and 68.7 ?10.2 kPa.s / L respectively. IG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 ?4.7 kPa and 158.4 ?25 kPa.s / L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin? level in the femoral artery increased by 20.9+ 7.1, 25.6?7.7, 28.6?7.9 pg / ml at the 60 th, 120th, 180th minute after the injection of L-NAME respectively (P<0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 ?.9 pg / 105 cells /ml (n=9). L-NAME increased endothelin-1 level to 42.8 ?4.9pg / 105 cells / ml (n = 9, P < 0.05) in case of 10-11 mol / L and to 43.0+ 4.7 pg / 105 cells / ml in case of 10 -7 mol/L (n=9, F<0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin? in vivo and in cultured vascular endothelial cells.
