To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR)Ca 2+ transport proteins and the mechanism of taurine(Tau) protecting cardiac muscle cells, 9 rabbits...To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR)Ca 2+ transport proteins and the mechanism of taurine(Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX , 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function , concentration of calcium in cardiomyocytes (Myo[Ca 2+ ] \%i\%), activity of SR Ca 2+ ATPase(SERCA2a), level of SERCA2a mRNA and Ca 2+ released channels(RYR2)mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca 2+ ATPase and level of SERCA2a mRNA decreased , while Myo[Ca 2+ ] \%i\% increased in DOX treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca 2+ ] \%i\% and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.展开更多
Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal ...Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg-1 were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond-back moth were 100% at 0.1 mg·kg-1. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond-back moth when the concentration was reduced to 0.05 mg·kg-1, which was higher than the commercialized Chlorantraniliprole.展开更多
Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,va...Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.展开更多
文摘To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR)Ca 2+ transport proteins and the mechanism of taurine(Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX , 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function , concentration of calcium in cardiomyocytes (Myo[Ca 2+ ] \%i\%), activity of SR Ca 2+ ATPase(SERCA2a), level of SERCA2a mRNA and Ca 2+ released channels(RYR2)mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca 2+ ATPase and level of SERCA2a mRNA decreased , while Myo[Ca 2+ ] \%i\% increased in DOX treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca 2+ ] \%i\% and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.
文摘Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg-1 were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond-back moth were 100% at 0.1 mg·kg-1. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond-back moth when the concentration was reduced to 0.05 mg·kg-1, which was higher than the commercialized Chlorantraniliprole.
基金supported by NIH grants(Grant Nos.HL-033333 and HL093671)to Shey-Shing Sheu
文摘Intracellular Ca2+ is vital for cell physiology.Disruption of Ca2+ homeostasis contributes to human diseases such as heart failure,neuron-degeneration,and diabetes.To ensure an effective intracellular Ca2+ dynamics,various Ca2+ transport proteins localized in different cellular regions have to work in coordination.The central role of mitochondrial Ca2+ transport mechanisms in responding to physiological Ca2+ pulses in cytosol is to take up Ca2+ for regulating energy production and shaping the amplitude and duration of Ca2+ transients in various micro-domains.Since the discovery that isolated mitochondria can take up large quantities of Ca2+ approximately 5 decades ago,extensive studies have been focused on the functional characterization and implication of ion channels that dictate Ca2+ transport across the inner mitochondrial membrane.The mitochondrial Ca2+ uptake sensitive to non-specific inhibitors ruthenium red and Ru360 has long been considered as the activity of mitochondrial Ca2+ uniporter(MCU) .The general consensus is that MCU is dominantly or exclusively responsible for the mitochondrial Ca2+ influx.Since multiple Ca2+ influx mechanisms(e.g.L-,T-,and N-type Ca2+ channel) have their unique functions in the plasma membrane,it is plausible that mitochondrial inner membrane has more than just MCU to decode complex intracellular Ca2+ signaling in various cell types.During the last decade,four molecular identities related to mitochondrial Ca2+ influx mechanisms have been identified.These are mitochondrial ryanodine receptor,mitochondrial uncoupling proteins,LETM1(Ca2+ /H+ exchanger) ,and MCU and its Ca2+ sensing regulatory subunit MICU1.Here,we briefly review recent progress in these and other reported mitochondrial Ca2+ influx pathways and their differences in kinetics,Ca2+ dependence,and pharmacological characteristics.Their potential physiological and pathological implications are also discussed.
