Lead (Pb) inhibited the activities of Na+ -K+ ATPase (IC50= 2.0×10^(-6) M), K + -Para-Nitrophenyl phosphatase (PNPPase) (IC50= 3.5×10^(-6) M) and [3H]-ouabain binding (IC50 = 4.0×10^(-5) M) in rat brain...Lead (Pb) inhibited the activities of Na+ -K+ ATPase (IC50= 2.0×10^(-6) M), K + -Para-Nitrophenyl phosphatase (PNPPase) (IC50= 3.5×10^(-6) M) and [3H]-ouabain binding (IC50 = 4.0×10^(-5) M) in rat brain P2 fraction. A variable temperature or pH significantly elevated the inhibition of Na+-K+ ATPase by Pb in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation of Na+ -K+ ATPase by ATP was indicated by a variation in Vmax values with no significant changes in Km values at any temperature studied. In the presence of Pb, for Na+ -K+ ATPase at pH 6.5 and 8.5, Vmax was decreased with an increase in Km values suggesting a mixed type of inhibition. Sulfhydryl agents such as dithiothreitol (DTT) and cvsteine (Cyst), but not glutathione (GSH) offered varied levels of protection against Pb-inhibition of Na + -K+ ATPase at pH 7.5 and 8.5. The present data suggest that inhibition of Na+ -K+ ATPase by Pb is both temperature and pH-dependent. These results also indicate that Pb inhibited Na + -K + ATPase by interfering with phosphorylation of enzyme molecule and dephosphorylation of the enzyme-phosphoryl complex and exerted an effect similar to that of SH-blocking agents.展开更多
Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase an...Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.展开更多
为研究盐度渐变对日本囊对虾的机体免疫的影响,实验设置了4个盐度梯度分别为26、22、18和14,统计了各盐度下日本囊对虾累计死亡率,检测了日本囊对虾体内血清总蛋白(TP)含量、碱性磷酸酶(AKP)和酸性磷酸酶(ACP)、血清ATP酶(Na^(+)/K^(+)-...为研究盐度渐变对日本囊对虾的机体免疫的影响,实验设置了4个盐度梯度分别为26、22、18和14,统计了各盐度下日本囊对虾累计死亡率,检测了日本囊对虾体内血清总蛋白(TP)含量、碱性磷酸酶(AKP)和酸性磷酸酶(ACP)、血清ATP酶(Na^(+)/K^(+)-ATPase和T-ATPase)、超氧化物歧化酶(SOD)和多酚氧化酶(PPO)的动态变化。结果显示,盐度渐变胁迫下各盐度组累计死亡率的大小为14>18>22>26,血清蛋白含量随胁迫强度的增加和胁迫时间的延长呈下降趋势,后随着盐度回升而上升。24~72 h ACP和AKP活力表现为盐度组14<18<22<26,且随时间的延长呈下降趋势,Na^(+)/K^(+)-ATPase和T-ATPase活力显示出盐度梯度差异显著,14盐度组显著高于其它盐度组(P<0.05),SOD活力与PPO活力受盐度胁迫强度和胁迫时间的影响显著,盐度胁迫强度越强,SOD活力与对照组的差异越显著(P<0.05),血清PPO活力的变化趋势越明显。日本囊对虾机体免疫受盐度胁迫显著,研究结果为日本囊对虾的健康养殖提供重要的理论指导及借鉴。展开更多
Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one ...Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one of the most important Ca2+regulators in the cell,the plasma membrane Ca2+-ATPase(PMCA),which has a high affinity for Ca2+and is widely expressed in brain.The ontogeny of PMCA isoforms,linked to specific requirements of Ca2+ during development of different brain areas,is addressed, as well as their function in the adult tissue.This is based on the high diversity of variants in the PMCA family in brain,which show particular kinetic differences possibly related to specific localizations and functions of the cell. Conversely,alterations in the activity of PMCAs could lead to changes in Ca2+homeostasis and,consequently,to neural dysfunction.The involvement of PMCA isoforms in certain neuropathologies and in brain ageing is also discussed.展开更多
文摘Lead (Pb) inhibited the activities of Na+ -K+ ATPase (IC50= 2.0×10^(-6) M), K + -Para-Nitrophenyl phosphatase (PNPPase) (IC50= 3.5×10^(-6) M) and [3H]-ouabain binding (IC50 = 4.0×10^(-5) M) in rat brain P2 fraction. A variable temperature or pH significantly elevated the inhibition of Na+-K+ ATPase by Pb in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation of Na+ -K+ ATPase by ATP was indicated by a variation in Vmax values with no significant changes in Km values at any temperature studied. In the presence of Pb, for Na+ -K+ ATPase at pH 6.5 and 8.5, Vmax was decreased with an increase in Km values suggesting a mixed type of inhibition. Sulfhydryl agents such as dithiothreitol (DTT) and cvsteine (Cyst), but not glutathione (GSH) offered varied levels of protection against Pb-inhibition of Na + -K+ ATPase at pH 7.5 and 8.5. The present data suggest that inhibition of Na+ -K+ ATPase by Pb is both temperature and pH-dependent. These results also indicate that Pb inhibited Na + -K + ATPase by interfering with phosphorylation of enzyme molecule and dephosphorylation of the enzyme-phosphoryl complex and exerted an effect similar to that of SH-blocking agents.
文摘Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.
文摘为研究盐度渐变对日本囊对虾的机体免疫的影响,实验设置了4个盐度梯度分别为26、22、18和14,统计了各盐度下日本囊对虾累计死亡率,检测了日本囊对虾体内血清总蛋白(TP)含量、碱性磷酸酶(AKP)和酸性磷酸酶(ACP)、血清ATP酶(Na^(+)/K^(+)-ATPase和T-ATPase)、超氧化物歧化酶(SOD)和多酚氧化酶(PPO)的动态变化。结果显示,盐度渐变胁迫下各盐度组累计死亡率的大小为14>18>22>26,血清蛋白含量随胁迫强度的增加和胁迫时间的延长呈下降趋势,后随着盐度回升而上升。24~72 h ACP和AKP活力表现为盐度组14<18<22<26,且随时间的延长呈下降趋势,Na^(+)/K^(+)-ATPase和T-ATPase活力显示出盐度梯度差异显著,14盐度组显著高于其它盐度组(P<0.05),SOD活力与PPO活力受盐度胁迫强度和胁迫时间的影响显著,盐度胁迫强度越强,SOD活力与对照组的差异越显著(P<0.05),血清PPO活力的变化趋势越明显。日本囊对虾机体免疫受盐度胁迫显著,研究结果为日本囊对虾的健康养殖提供重要的理论指导及借鉴。
基金Supported by Grants No.BFU2008-00182 from MICINN,Fundación Marcelino Botín,Spain(to Mata AM)Sepulveda MR received a Postdoctoral Fellowship from Programa de Reincorpo-ración de Doctores,Junta de Extremadura,Spain
文摘Calcium signaling is used by neurons to control a variety of functions,including cellular differentiation,synaptic maturation,neurotransmitter release,intracellular signaling and cell death.This review focuses on one of the most important Ca2+regulators in the cell,the plasma membrane Ca2+-ATPase(PMCA),which has a high affinity for Ca2+and is widely expressed in brain.The ontogeny of PMCA isoforms,linked to specific requirements of Ca2+ during development of different brain areas,is addressed, as well as their function in the adult tissue.This is based on the high diversity of variants in the PMCA family in brain,which show particular kinetic differences possibly related to specific localizations and functions of the cell. Conversely,alterations in the activity of PMCAs could lead to changes in Ca2+homeostasis and,consequently,to neural dysfunction.The involvement of PMCA isoforms in certain neuropathologies and in brain ageing is also discussed.
