Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondr...Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I2, displaying high similarity of sequence with monoamine oxidase-B （MAO-B）, is structurally related to MAO-B, but the I2 imidazoline binding site （IEBS） with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibriUary acidic protein （GFAP） in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamateinduced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate （NMDA） receptor, inhibiting all isoforms of nitric oxide synthase （NOS）, and selectively blocking the voltage-gated calcium channels （VGCC）. It would be expected that agmatine is one of the potential neuroprotective agents.展开更多
Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the...Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.展开更多
Background: Polyamines stimulate DNA transcription and m RNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and...Background: Polyamines stimulate DNA transcription and m RNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and survival of conceptuses(embryo/fetus and placenta). The ovine conceptus produces polyamines via classical and non-classical pathways. In the classical pathway, arginine(Arg) is transformed into ornithine, which is then decarboxylated by ornithine decarboxylase(ODC1) to produce putrescine which is the substrate for the production of spermidine and spermine. In the non-classical pathway, Arg is converted to agmatine(Agm) by arginine decarboxylase(ADC), and Agm is converted to putrescine by agmatinase(AGMAT).Methods: Morpholino antisense oligonucleotides(MAOs) were designed and synthesized to inhibit translational initiation of the m RNAs for ODC1 and ADC, in ovine conceptuses.Results: The morphologies of MAO control, MAO-ODC1, and MAO-ADC conceptuses were normal. Double knockdown of ODC1 and ADC(MAO-ODC1:ADC) resulted in two phenotypes of conceptuses; 33% of conceptuses appeared to be morphological y and functional y normal(phenotype a) and 67% of the conceptuses presented an abnormal morphology and functionality(phenotype b). Furthermore, MAO-ODC1:ADC(a) conceptuses had greater tissue concentrations of Agm,putrescine, and spermidine than MAO control conceptuses, while MAO-ODC1:ADC(b) conceptuses only had greater tissue concentrations of Agm. Uterine flushes from ewes with MAO-ODC1:ADC(a) had greater amounts of arginine, aspartate, tyrosine, citrulline, lysine, phenylalanine, isoleucine, leucine, and glutamine, while uterine flushes of ewes with MAO-ODC1:ADC(b) conceptuses had lower amount of putrescine, spermidine, spermine, alanine, aspartate,glutamine, tyrosine, phenylalanine, isoleucine, leucine, and lysine.Conclusions: The double-knockdown of translation of ODC1 and ADC m RNAs was most detrimental to conceptus development and their production of interferon tau(IFNT). Agm, polyamines, amino acids,展开更多
A new method for the enzymatic synthesis of agmatine by immobilized Escherichia coli cells with arginine decarboxylase（ADC） activity was established and a series of optimal reaction conditions was set down. The argi...A new method for the enzymatic synthesis of agmatine by immobilized Escherichia coli cells with arginine decarboxylase（ADC） activity was established and a series of optimal reaction conditions was set down. The arginine decarboxylase showed the maximum activity when the pyridoxal phosphate（PLP） concentration was 50 mmol/L, pH=7 and 45 °C. The arginine decarboxylase exhibited the maximum production efficiency when the substrate concentration was 100 mmol/L and the reaction time was 15 h. It was also observed that the appropriate concentration of Mg2＋, especially at 0.5 mmol/L promoted the arginine decarboxylase activity; Mn2＋ had little effect on the arginine decarboxylase activity. The inhibition of Cu2＋ and Zn2＋ to the arginine decarboxylase activity was significant. The immobilized cells were continuously used 6 times and the average conversion rate during the six-time usage was 55.6%. The immobilized cells exhibited favourable operational stability. After optimization, the maximally cumulative amount of agmatine could be up to 20 g/L. In addition, this method can also catalyze D,L-arginine to agmatine, leaving the pure optically D-arginine simultaneously. The method has a very important guiding significance to the enzymatic preparation of agmatine.展开更多
基金This work was supported by the National Natural Science Foundation of China （No. 30470611）the Natural Science Foundation of Zhejiang province （No.Y204133）.
文摘Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I2, displaying high similarity of sequence with monoamine oxidase-B （MAO-B）, is structurally related to MAO-B, but the I2 imidazoline binding site （IEBS） with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibriUary acidic protein （GFAP） in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamateinduced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate （NMDA） receptor, inhibiting all isoforms of nitric oxide synthase （NOS）, and selectively blocking the voltage-gated calcium channels （VGCC）. It would be expected that agmatine is one of the potential neuroprotective agents.
基金supported by grants from the National Basic Research Development Program of China (2015CB553504)the National Natural Science Foundation of China (30930040 and 81102426)a Project of the National Science and Technology Support Program of China(2012BAI01B07)
文摘Abstract Chronic exposure to opioids induces adaptation of glutamate neurotransmission, which plays a crucial role in addiction. Our previous studies revealed that agmatine attenuates opioid addiction and prevents the adaptation of glutamate neurotransmission in the nucleus accumbens of chronic morphine-treated rats. The hippocampus is important for drug addiction; however, whether adaptation of glutamate neurotransmission is modulated by agmatine in the hippocampus remains unknown. Here, we found that continuous pretreatment of rats with ascending doses of morphine for 5 days resulted in an increase in the hip- pocampal extracellular glutamate level induced by nalox- one （2 mg/kg, i.p.） precipitation. Agmatine （20 mg/kg, s.c.） administered concurrently with morphine for 5 days attenuated the elevation of extracellular glutamate levels induced by naloxone precipitation. Furthermore, in the hippocampal synaptosome model, agmatine decreased the release and increased the uptake of glutamate in synapto- somes from chronic morphine-treated rats, which might contribute to the reduced elevation of glutamate levels induced by agrnatine. We also found that expression of the hippocampal NR2B subunit, rather than the NR1 subunit, of N-methyl-D-aspartate receptors （NMDARs） was down-regulated after chronic morphine treatment, and agmatine inhibited this reduction. Taken together, agmatine pre- vented the adaptation of the hippocampal glutamate system caused by chronic exposure to morphine, including mod- ulating extracellular glutamate concentration and NMDAR expression, which might be one of the mechanisms underlying the attenuation of opioid addiction by agmatine.
基金supported primarily by the Agriculture and Food Research Initiative Competitive Grants(2016-67,015-24,958 to Fuller W.Bazer and 2015-67,015-23,276 to Guoyao Wu)from the United States Department of Agriculture,National Institute of Food and Agriculturesupported by funding from the Sustainability Strategy2013–2014,from CODI University of Antioquia(Ude A),Medellín,Colombia Scholarship“Becas Doctorado Ude A 2014.”
文摘Background: Polyamines stimulate DNA transcription and m RNA translation for protein synthesis in trophectoderm cells, as well as proliferation and migration of cells; therefore, they are essential for development and survival of conceptuses(embryo/fetus and placenta). The ovine conceptus produces polyamines via classical and non-classical pathways. In the classical pathway, arginine(Arg) is transformed into ornithine, which is then decarboxylated by ornithine decarboxylase(ODC1) to produce putrescine which is the substrate for the production of spermidine and spermine. In the non-classical pathway, Arg is converted to agmatine(Agm) by arginine decarboxylase(ADC), and Agm is converted to putrescine by agmatinase(AGMAT).Methods: Morpholino antisense oligonucleotides(MAOs) were designed and synthesized to inhibit translational initiation of the m RNAs for ODC1 and ADC, in ovine conceptuses.Results: The morphologies of MAO control, MAO-ODC1, and MAO-ADC conceptuses were normal. Double knockdown of ODC1 and ADC(MAO-ODC1:ADC) resulted in two phenotypes of conceptuses; 33% of conceptuses appeared to be morphological y and functional y normal(phenotype a) and 67% of the conceptuses presented an abnormal morphology and functionality(phenotype b). Furthermore, MAO-ODC1:ADC(a) conceptuses had greater tissue concentrations of Agm,putrescine, and spermidine than MAO control conceptuses, while MAO-ODC1:ADC(b) conceptuses only had greater tissue concentrations of Agm. Uterine flushes from ewes with MAO-ODC1:ADC(a) had greater amounts of arginine, aspartate, tyrosine, citrulline, lysine, phenylalanine, isoleucine, leucine, and glutamine, while uterine flushes of ewes with MAO-ODC1:ADC(b) conceptuses had lower amount of putrescine, spermidine, spermine, alanine, aspartate,glutamine, tyrosine, phenylalanine, isoleucine, leucine, and lysine.Conclusions: The double-knockdown of translation of ODC1 and ADC m RNAs was most detrimental to conceptus development and their production of interferon tau(IFNT). Agm, polyamines, amino acids,
基金Supported by the National Technology-Innovation Fund of China(No.02CJ-13-01-16)
文摘A new method for the enzymatic synthesis of agmatine by immobilized Escherichia coli cells with arginine decarboxylase（ADC） activity was established and a series of optimal reaction conditions was set down. The arginine decarboxylase showed the maximum activity when the pyridoxal phosphate（PLP） concentration was 50 mmol/L, pH=7 and 45 °C. The arginine decarboxylase exhibited the maximum production efficiency when the substrate concentration was 100 mmol/L and the reaction time was 15 h. It was also observed that the appropriate concentration of Mg2＋, especially at 0.5 mmol/L promoted the arginine decarboxylase activity; Mn2＋ had little effect on the arginine decarboxylase activity. The inhibition of Cu2＋ and Zn2＋ to the arginine decarboxylase activity was significant. The immobilized cells were continuously used 6 times and the average conversion rate during the six-time usage was 55.6%. The immobilized cells exhibited favourable operational stability. After optimization, the maximally cumulative amount of agmatine could be up to 20 g/L. In addition, this method can also catalyze D,L-arginine to agmatine, leaving the pure optically D-arginine simultaneously. The method has a very important guiding significance to the enzymatic preparation of agmatine.
