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Guiqin Xie - One of the best experts on this subject based on the ideXlab platform.
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JPET#186833 1
2016Co-Authors: Guiqin Xie, Wanhong Zuo, Ana Polache, Luis Granero, Lucia Hipólito, Krešimir KrnjevićAbstract:Salsolinol stimulates dopamine neurons in slices of posterior VTA indirectly by activating μ-opioid receptor
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Salsolinol-induced stimulation of dopaminergic (DA) neurons is attenuated by APV and DNQX.
2013Co-Authors: Guiqin XieAbstract:A1, Traces illustrate spike discharge at the times indicated in A2. A2, Time course of the increase in the ongoing pacemaking firing rate, recorded from a current-clamped DA neuron in the posterior ventral tegmental area (p-VTA) of a rat, by 0.1 µM salsolinol. B1, Traces obtained at the times indicated in B2. B2, Time course of the effect of salsolinol on the firing rate of a DA neuron in the presence of APV (50 µM) and DNQX (20 µM), the antagonists of NMDA and AMPA receptors. C, Summary plot of decease in firing rate by APV + DNQX. D, Summary plot (means ± S.E.M.) of increase in firing rate of p-VTA DA neurons induced by salsolinol (0.1 µM) in ACSF is larger than that in the APV+DNQX. Numbers in bars indicate numbers of neurons tested. *P
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Salsolinol modulation of dopamine neurons
Frontiers in Behavioral Neuroscience, 2013Co-Authors: Guiqin Xie, Krešimir KrnjevićAbstract:Salsolinol, a tetrahydroisoquinoline present in the human and rat brains, is the condensation product of dopamine and acetaldehyde, the first metabolite of ethanol. Previous evidence obtained in vivo links salsolinol with the mesolimbic dopaminergic system: salsolinol is self-administered into the posterior of the ventral tegmental area (pVTA) of rats; intra-VTA administration of salsolinol induces a strong conditional place preference and increases dopamine release in the nucleus accumbens. However, the underlying neuronal mechanisms are unclear. Here we present an overview of some of the recent research on this topic. Electrophysiological studies reveal that dopaminergic neurons in the posterior ventral tegmental area (pVTA) are a target of salsolinol. In acute brain slices from rats, salsolinol increases the excitability and accelerates the ongoing firing of dopamine neurons in the pVTA. Intriguingly, this action of salsolinol involves multiple pre- and post-synaptic mechanisms, including: (a) depolarizing the membrane potential of dopamine neurons; (b) activating mu opioid receptors on the GABAergic inputs to dopamine neurons, which decreases GABAergic activity and dopamine neurons are disinhibited; and (c) enhancing presynaptic glutamatergic transmission onto dopamine neurons via activation of dopamine type 1 receptors, probably situated on the glutamatergic terminals. These novel mechanisms may contribute to the rewarding/reinforcing properties of salsolinol observed in vivo.
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The D1R antagonist SKF 83566 eliminates salsolinol's augmentation of eEPSCs.
2013Co-Authors: Guiqin XieAbstract:A, Current traces show that salsolinol did not change the amplitude of eEPSC1 and PPR in the presence of 10 µM SKF 83566. B, Time course of salsolinol-induced changes of eEPSC1 amplitude in nine experiments. C, Summary of salsolinol-induced changes (%) in eEPSC1 amplitude and PPR in the presence of SKF 83566 (data from nine cells). *P
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Salsolinol increases amplitude and decreases paired-pulse ratio (PPR) of evoked EPSCs (eEPSCs) recorded from p-VTA DA neurons.
2013Co-Authors: Guiqin XieAbstract:eEPSCs were recorded in the presence of bicuculline (10 µM) at a holding potential of −70 mV. A, Salsolinol (0.1 µM) sharply increased the peak amplitude of eEPSC1 and had minimal effect on that of eEPSC2 evoked by paired stimulation (at 50- ms interval) within the VTA, and hence reduced the PPR (EPSC2/EPSC1). B, Time course of salsolinol-induced enhancement of eEPSC1 amplitude in one experiment. C, Summary of salsolinol-induced changes (%) in eEPSC1 amplitude and PPR (Mean ± SEM, from eleven neurons). *P
Wakako Maruyama - One of the best experts on this subject based on the ideXlab platform.
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dopamine derived salsolinol derivatives as endogenous monoamine oxidase inhibitors occurrence metabolism and function in human brains
Neurotoxicology, 2004Co-Authors: Makoto Naoi, Wakako Maruyama, Georgy M NagyAbstract:Abstract Salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, is an endogenous catechol isoquinoline detected in humans by M. Sandler. In human brain, a series of catechol isoquinolines were identified as the condensation products of dopamine or other monoamines with aldehydes or keto-acids. Recently selective occurrence of the ( R )enantiomers of salsolinol derivatives was confirmed in human brain, and they are synthesized by enzymes in situ, but not by the non-enzymatic Pictet–Spengler reaction. A ( R )salsolinol synthase catalyzes the enantio-specific synthesis of ( R )salsolinol from dopamine and acetaldehyde, and ( R )salsolinol N -methyltransferase synthesizes N -methyl( R )salsolinol, which is further oxidized into 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion by non-enzymatic and enzymatic oxidation. The step-wise reactions, N -methylation and oxidation, induce the specified distribution of the N -methylated and oxidized derivatives in the human nigro-striatum, suggesting that these derivatives may be involved in the function of dopamine neurons under physiological and pathological conditions. As shown by in vivo and in vitro experiments, salsolinol derivatives affect the levels of monoamine neurotransmitters though the inhibition of enzymes related in the metabolism of catechol- and indoleamines. In addition, the selective neurotoxicity of N -methyl( R )salsolinol to dopamine neurons was confirmed by preparation of an animal model of Parkinson’s disease in rats. The involvement of N -methyl( R )salsolinol in the pathogenesis of Parkinson’s disease was further indicated by the increase in the N -methyl( R )salsolinol levels in the cerebrospinal fluid and that in the activity of its synthesizing enzyme, a neural ( R )salsolinol N -methyltransferase, in the lymphocytes prepared from parkinsonian patients. N -Methyl( R )salsolinol induces apoptosis in dopamine neurons, which is mediated by death signal transduction in mitochondria. In addition, salsolinol was found to function as a signal transmitter for the prolactin release in the neuro-intermediate lobe of the brain. These results are discussed in relation to role of dopamine-derived endogenous salsolinol derivatives as the regulators of neurotransmission, dopaminergic neurotoxins and neuro-hormonal transmitters in the human brain.
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an anti parkinson s disease drug n propargyl 1 r aminoindan rasagiline enhances expression of anti apoptotic bcl 2 in human dopaminergic sh sy5y cells
Neuroscience Letters, 2002Co-Authors: Yukihiro Akao, Masayo Shamotonagai, Wakako Maruyama, Hong Yi, Moussa B H Youdim, Makato NaoiAbstract:Abstract N-Propargyl-1(R)-aminoindan (rasagiline) is now under phase III clinical trials for Parkinson's disease (PD), and it rescues dopamine neurons from cell death in animal and cellular models of PD. Recently, we proved that rasagiline protected dopaminergic SH-SY5Y cells against apoptosis induced by a dopaminergic neurotoxin, N-methyl(R)salsolinol, and the mechanism was clarified to be due to suppression of death signal transduction in mitochondria. In this paper, the effects of rasagiline on the levels of anti-apoptotic bcl-2 gene family were studied. Rasagiline increased the levels of bcl-2 and bcl-xl mRNA at 100–10 nM and 100–10 pM, but not the level of pro-apoptotic bax mRNA. Enhanced expression of bcl-2 family indicates the ability of rasagiline to adjust the apoptotic threshold and protect degenerating neurons in PD.
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transfection enforced bcl 2 overexpression and an anti parkinson drug rasagiline prevent nuclear accumulation of glyceraldehyde 3 phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin n methyl r salsolinol
Journal of Neurochemistry, 2001Co-Authors: Wakako Maruyama, Yukihiro Akao, Moussa B H Youdim, Bruce A Davis, Makoto NaoiAbstract:An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, was found to induce apoptosis in human dopaminergic SH-SY5Y cells by step-wise activation of apoptotic cascade; collapse in mitochondrial membrane potential, ΔΨm, activation of caspases, and fragmentation of DNA. Recently, accumulation of gylceraldehyde-3-phosphate dehydrogenase (GAPDH) in nuclei was proposed to play an important role in apoptosis. In this paper, involvement of GAPDH in apoptosis induced by N-methyl(R)salsolinol was studied. The isoquinoline reduced ΔΨm within 3 h, as detected by a fluorescence indicator, JC-1, then after 16 h incubation, GAPDH accumulated in nuclei by detection with immunostaining. To clarify the role of GAPDH in apoptotic process, a stable cell line of Bcl-2 overexpressed SH-SY5Y cells was established. Overexpression of Bcl-2 prevented the decline in ΔΨm and also apoptotic DNA damage induced by N-methyl(R)salsolinol. In Bcl-2 transfected cells, nuclear translocation of GAPDH was also completely suppressed. In addition, a novel antiparkinsonian drug, rasagiline, prevented nuclear accumulation of GAPDH induced by N-methyl(R)salsolinol in control cells. These results suggest that GAPDH may accumulate in nuclei as a consequence of signal transduction, which is antagonized by anti-apoptotic Bcl-2 protein family and rasagiline. The results are discussed in concern to intracellular mechanism underlying anti-apoptotic function of rasagiline analogues.
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neurotoxins induce apoptosis in dopamine neurons protection by n propargylamine 1 r and s aminoindan rasagiline and tv1022
Journal of Neural Transmission-supplement, 2000Co-Authors: Wakako Maruyama, Yukihiro Akao, Moussa B H Youdim, Makoto NaoiAbstract:In Parkinson’s disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N-methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, AtPm. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bc1-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved O’Pm, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline.
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assay for the r and s enantiomers of salsolinols in biological samples and foods with ion pair high performance liquid chromatography using β cyclodextrin as a chiral mobile phase additive
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: Yulin Deng, Wakako Maruyama, Masao Kawai, Philippe Dostert, Hatsuo Yamamura, Tsutomu Takahashi, Makoto NaoiAbstract:A chromatographic procedure was devised for the quantitative determination of the enantiomers of salsolinol and N-methylsalsolinol, which are biologically important alkaloids. The enantiomers of salsolinol and N-methylsalsolinol were completely separated using β-cyclodextrin in a reversed-phase ion-pair system. The HPLC method was sensitive enough to detect the isoquinolines at a concentration less than 0.1 pmol per injection. The presence of (R)- and (S)-salsolinol was confirmed in fermented foods and beverages, while N-methylsalsolinol was not detected. On the other hand, the (R)-enantiomers of both salsolinol and N-methylsalsolinol were found to predominate in the human brain.
Lucyna Antkiewicz-michaluk - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL ARTICLE Chronic Salsolinol Administration Prevents the Behavioral and Neurochemical Effects of L-DOPA in Rats
2016Co-Authors: Jerzy Michaluk, Lucyna Antkiewicz-michalukAbstract:Abstract 1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroiso-quinoline (salsolinol) is a well-known endogenous compound that has been proposed as a factor involved in the patho-genesis of Parkinson’s disease. In the present study, we in-vestigated the impact of acute and chronic salsolinol (100 mg.kg i.p.) administration on L-DOPA-induced loco-motor hyperactivity and neurochemical changes (the dopa-mine level and its metabolism in rat brain structures). Moreover, using the in vivo microdialysis technique, we measured the effect of acute and chronic salsolinol injection on L-DOPA-induced dopamine release in the rat striatum. The behavioral data demonstrated that both acute and chronic salsolinol administration antagonized L-DOPA-mediated hyperactivity. An ex vivo neurochemical experiment indi-cated that chronic but not acute salsolinol administratio
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ORIGINAL ARTICLE Salsolinol, an Endogenous Compound Triggers a Two-Phase Opposing Action in the Central Nervous System
2016Co-Authors: Małgorzata Kajta, Tomasz Lenda, Lucyna Antkiewicz-michalukAbstract:rahydroisoquinoline), an endogenous compound present in the brain, was suspected of participation in the etiopatho-genesis of Parkinson’s disease, the most common serious movement disorder worldwide. In this study, we evaluated the effect of different (50, 100, and 500 lM) concentra-tions of salsolinol on markers of glutamate-induced apop-totic and neurotoxic cell damage, such as caspase-3 activity, lactate dehydrogenase (LDH) release, and the loss of mitochondrial membrane potential. Biochemical data were complemented with the cellular analysis, including Hoechst 33342 and calcein AM staining, to visualize apoptotic DNA-fragmentation and to assess cell survival, respectively. The assessment of all investigated parameters was performed in primary cultures of rat or mouse hippo-campal and striatum cells. Our study showed that salsolino
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Salsolinol, an Endogenous Compound Triggers a Two-Phase Opposing Action in the Central Nervous System
Neurotoxicity Research, 2015Co-Authors: Edyta Możdżeń, Małgorzata Kajta, Agnieszka Wąsik, Tomasz Lenda, Lucyna Antkiewicz-michalukAbstract:Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), an endogenous compound present in the brain, was suspected of participation in the etiopathogenesis of Parkinson’s disease, the most common serious movement disorder worldwide. In this study, we evaluated the effect of different (50, 100, and 500 µM) concentrations of salsolinol on markers of glutamate-induced apoptotic and neurotoxic cell damage, such as caspase-3 activity, lactate dehydrogenase (LDH) release, and the loss of mitochondrial membrane potential. Biochemical data were complemented with the cellular analysis, including Hoechst 33342 and calcein AM staining, to visualize apoptotic DNA-fragmentation and to assess cell survival, respectively. The assessment of all investigated parameters was performed in primary cultures of rat or mouse hippocampal and striatum cells. Our study showed that salsolinol had biphasic effects, namely, at lower concentrations (50 and 100 µM), it demonstrated a distinct neuroprotective activity, whereas in the highest one (500 µM) caused neurotoxic effect. Salsolinol in concentrations of 50 and 100 µM significantly antagonized the pro-apoptotic and neurotoxic effects caused by 1 mM glutamate. Salsolinol diminished the number of bright fragmented nuclei with condensed chromatin and increased cell survival in Hoechst 33342 and calcein AM staining in hippocampal cultures. Additionally, in the low 50 µM concentration, it produced a significant inhibition of glutamate-induced loss of membrane mitochondrial potential. Only the highest concentration of salsolinol (500 µM) enhanced the glutamate excitotoxicity. Ex vivo studies indicated that both acute and chronic administration of salsolinol did not affect the dopamine metabolism, its striatal concentration or α-synuclein and tyrosine hydroxylase protein level in the rat substantia nigra and striatum. Summarizing, the present studies exclude possibility that salsolinol under physiological conditions could be an endogenous factor involved in the neurogenerative processes; conversely, it can exert a protective action on nerve cells in the brain. These findings may have important implications for the development of the new strategies to treat or prevent neural degeneration.
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LECTURES 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES AS ENDOGENOUS REGULATORS OF DOPAMINERGIC ACTIVITY IN CNS WITH NEUROPROTECTIVE ACTION
2014Co-Authors: Lucyna Antkiewicz-michalukAbstract:derivatives present in the brain are endogenous. The most investigated of these compounds is 1-methyl-6,7,-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), which in mammalian brain is a product of enzymatic condensation of dopamine (DA) with acetaldehyde [13]. Salsolinol is present in the human brain, particularly in alcoholics, where the availability of acetaldehyde is higher. In a clinical study, we have found that the concentration of salsolinol in the cerebrospinal fluid of parkinsonian patients with advanced parkinsonism was significantly augmented and this increase was positively correlated with the degree of motor disability and dementia [5]. The suspicions that TIQs may be neurotoxic resulted from their similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and ability to form tetrahydroisoquinolinium ions, analogous to 1-methyl-4-phenylpyridinium ion (MPP +), and in fact experimental parkinsonism was induced by TIQs in marmosets and rodents [15, 16]. While MPTP acts rapidly and produces irreversible neurotoxic changes after a single injection [6, 7], TIQs do not produce an immediate neurotoxicity. In the animal experiment, we have found that TIQs (1,2,3,4tetrahydroisoquinoline, TIQ; 1-benzyl-1,2,3,4-tetrahydroisoquinoline, 1BnTIQ; and salsolinol) must be given at high doses repeatedly for at least three weeks to induce rather weak neurotoxic effects [2, 4, 12]. Recently, the interest of researchers was attracted by two endogenous derivatives: 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) and 1Bn-TIQ. 1MeTIQ was regarded as a neuroprotectant [18, 21], whereas 1BnTIQ was described as having neurotoxic properties [10, 11]. Apart from the propensity to form quaternary ions, the neurodegenerative effects of TIQs may be caused by the facilitation of DA metabolism and catabolism by N-oxidation. The oxidative MAOdependent pathway of DA catabolism to form 3,4dihydroxyphenylacetic acid (DOPAC) is associated with a subsequent production of hydrogen peroxid
Makoto Naoi - One of the best experts on this subject based on the ideXlab platform.
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dopamine derived salsolinol derivatives as endogenous monoamine oxidase inhibitors occurrence metabolism and function in human brains
Neurotoxicology, 2004Co-Authors: Makoto Naoi, Wakako Maruyama, Georgy M NagyAbstract:Abstract Salsolinol, 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, is an endogenous catechol isoquinoline detected in humans by M. Sandler. In human brain, a series of catechol isoquinolines were identified as the condensation products of dopamine or other monoamines with aldehydes or keto-acids. Recently selective occurrence of the ( R )enantiomers of salsolinol derivatives was confirmed in human brain, and they are synthesized by enzymes in situ, but not by the non-enzymatic Pictet–Spengler reaction. A ( R )salsolinol synthase catalyzes the enantio-specific synthesis of ( R )salsolinol from dopamine and acetaldehyde, and ( R )salsolinol N -methyltransferase synthesizes N -methyl( R )salsolinol, which is further oxidized into 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion by non-enzymatic and enzymatic oxidation. The step-wise reactions, N -methylation and oxidation, induce the specified distribution of the N -methylated and oxidized derivatives in the human nigro-striatum, suggesting that these derivatives may be involved in the function of dopamine neurons under physiological and pathological conditions. As shown by in vivo and in vitro experiments, salsolinol derivatives affect the levels of monoamine neurotransmitters though the inhibition of enzymes related in the metabolism of catechol- and indoleamines. In addition, the selective neurotoxicity of N -methyl( R )salsolinol to dopamine neurons was confirmed by preparation of an animal model of Parkinson’s disease in rats. The involvement of N -methyl( R )salsolinol in the pathogenesis of Parkinson’s disease was further indicated by the increase in the N -methyl( R )salsolinol levels in the cerebrospinal fluid and that in the activity of its synthesizing enzyme, a neural ( R )salsolinol N -methyltransferase, in the lymphocytes prepared from parkinsonian patients. N -Methyl( R )salsolinol induces apoptosis in dopamine neurons, which is mediated by death signal transduction in mitochondria. In addition, salsolinol was found to function as a signal transmitter for the prolactin release in the neuro-intermediate lobe of the brain. These results are discussed in relation to role of dopamine-derived endogenous salsolinol derivatives as the regulators of neurotransmission, dopaminergic neurotoxins and neuro-hormonal transmitters in the human brain.
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transfection enforced bcl 2 overexpression and an anti parkinson drug rasagiline prevent nuclear accumulation of glyceraldehyde 3 phosphate dehydrogenase induced by an endogenous dopaminergic neurotoxin n methyl r salsolinol
Journal of Neurochemistry, 2001Co-Authors: Wakako Maruyama, Yukihiro Akao, Moussa B H Youdim, Bruce A Davis, Makoto NaoiAbstract:An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, was found to induce apoptosis in human dopaminergic SH-SY5Y cells by step-wise activation of apoptotic cascade; collapse in mitochondrial membrane potential, ΔΨm, activation of caspases, and fragmentation of DNA. Recently, accumulation of gylceraldehyde-3-phosphate dehydrogenase (GAPDH) in nuclei was proposed to play an important role in apoptosis. In this paper, involvement of GAPDH in apoptosis induced by N-methyl(R)salsolinol was studied. The isoquinoline reduced ΔΨm within 3 h, as detected by a fluorescence indicator, JC-1, then after 16 h incubation, GAPDH accumulated in nuclei by detection with immunostaining. To clarify the role of GAPDH in apoptotic process, a stable cell line of Bcl-2 overexpressed SH-SY5Y cells was established. Overexpression of Bcl-2 prevented the decline in ΔΨm and also apoptotic DNA damage induced by N-methyl(R)salsolinol. In Bcl-2 transfected cells, nuclear translocation of GAPDH was also completely suppressed. In addition, a novel antiparkinsonian drug, rasagiline, prevented nuclear accumulation of GAPDH induced by N-methyl(R)salsolinol in control cells. These results suggest that GAPDH may accumulate in nuclei as a consequence of signal transduction, which is antagonized by anti-apoptotic Bcl-2 protein family and rasagiline. The results are discussed in concern to intracellular mechanism underlying anti-apoptotic function of rasagiline analogues.
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neurotoxins induce apoptosis in dopamine neurons protection by n propargylamine 1 r and s aminoindan rasagiline and tv1022
Journal of Neural Transmission-supplement, 2000Co-Authors: Wakako Maruyama, Yukihiro Akao, Moussa B H Youdim, Makoto NaoiAbstract:In Parkinson’s disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N-methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, AtPm. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bc1-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved O’Pm, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline.
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assay for the r and s enantiomers of salsolinols in biological samples and foods with ion pair high performance liquid chromatography using β cyclodextrin as a chiral mobile phase additive
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: Yulin Deng, Wakako Maruyama, Masao Kawai, Philippe Dostert, Hatsuo Yamamura, Tsutomu Takahashi, Makoto NaoiAbstract:A chromatographic procedure was devised for the quantitative determination of the enantiomers of salsolinol and N-methylsalsolinol, which are biologically important alkaloids. The enantiomers of salsolinol and N-methylsalsolinol were completely separated using β-cyclodextrin in a reversed-phase ion-pair system. The HPLC method was sensitive enough to detect the isoquinolines at a concentration less than 0.1 pmol per injection. The presence of (R)- and (S)-salsolinol was confirmed in fermented foods and beverages, while N-methylsalsolinol was not detected. On the other hand, the (R)-enantiomers of both salsolinol and N-methylsalsolinol were found to predominate in the human brain.
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a novel enzyme enantio selectively synthesizes r salsolinol a precursor of a dopaminergic neurotoxin n methyl r salsolinol
Neuroscience Letters, 1996Co-Authors: Makoto Naoi, Wakako Maruyama, Philippe Dostert, Kohfuku Kohda, Toyo KaiyaAbstract:In the human brain, only (R)enantiomer of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline ((R)salsolinol) and N-methyl-salsolinol, a dopaminergic neurotoxin, were detected, suggesting their enzymatic biosynthesis. This paper reports the isolation and characterization of a novel enzyme, which enantio-selectively synthesizes (R)salsolinol from dopamine and acetaldehyde. Dopamine, acetaldehyde, formaldehyde and pyruvic acid were the substrates of this synthase, whereas N-methyldopamine, adrenaline, noradrenaline and L-DOPA were not. The possible function of this enzyme under physiological and pathological conditions in the brain is discussed.
Gilberto De Nucci - One of the best experts on this subject based on the ideXlab platform.
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Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum.
PloS one, 2017Co-Authors: Rafael Campos, Marco Antonio De Oliveira, Renata Lopes Rodrigues, Julio Alejandro Rojas-moscoso, José Carlos Cogo, Edson Antunes, Fabíola Z. Mónica, Ronilson Agnaldo Moreno, Gilberto De NucciAbstract:Reptiles are the first amniotes to develop an intromitent penis, however until now the mechanisms involved in the electrical field stimulation-induced contraction on corpora cavernosa isolated from Crotalus durissus terrificus were not investigated. Crotalus and rabbit corpora cavernosa were mounted in 10 mL organ baths for isometric tension recording. Electrical field stimulation (EFS)-induced contractions were performed in presence/absence of phentolamine (10 μM), guanethidine (30 μM), tetrodotoxin (1 μM and 1mM), A-803467 (10 μM), 3-iodo-L-Tyrosine (1 mM), salsolinol (3 μM) and a modified Krebs solution (equimolar substitution of NaCl by N-methyl-D-glucamine). Immuno-histochemistry for tyrosine hydroxylase was also performed. Electrical field stimulation (EFS; 8 Hz and 16 Hz) caused contractions in both Crotalus and rabbit corpora cavernosa. The contractions were abolished by previous incubation with either phentolamine or guanethidine. Tetrodotoxin (1 μM) also abolished the EFS-induced contractions of rabbit CC, but did not affect EFS-induced contractions of Crotalus CC. Addition of A-803467 (10 μM) did not change the EFS-induced contractions of Crotalus CC but abolished rabbit CC contractions. 3-iodo-L-Tyrosine and salsolinol had no effect on EFS-induced contractions of Crotalus CC and Rabbit CC. Replacement of NaCl by N- Methyl-D-glucamine (NMDG) abolished EFS-induced contractions of rabbit CC, but did not affect Crotalus CC. The presence of tyrosine hydroxylase was identified in endothelial cells only of Crotalus CC. Since the EFS-induced contractions of Crotalus CC is dependent on catecholamine release, insensitive to TTX, insensitive to A803467 and to NaCl replacement, it indicates that the source of cathecolamine is unlikely to be from adrenergic terminals. The finding that tyrosine hydroxylase is present in endothelial cells suggests that these cells can modulate Crotalus CC tone.
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Tetrodotoxin-insensitive electrical field stimulation-induced contractions on Crotalus durissus terrificus corpus cavernosum - Fig 5
2017Co-Authors: Rafael Campos, Marco Antonio De Oliveira, Renata Lopes Rodrigues, Julio Alejandro Rojas-moscoso, José Carlos Cogo, Edson Antunes, Fabíola Z. Mónica, Ronilson Agnaldo Moreno, Gilberto De NucciAbstract:Representative illustration of EFS-induced contraction of Crotalus (A) and rabbit (B) corpora cavernosa in the presence of salsolinol (3 μM).
