Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons

Naoi, Makoto; Maruyama, Wakako; Akao, Y.; Zhang, Jin; Parvez, H.

doi:10.1016/s0300-483x(00)00309-7

Cited by 54 publications

(45 citation statements)

References 80 publications

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“…In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected mice Bax expression levels were increased in regions specifically affected by the neurodegeneration processes [39,40]. So far, Naoi et al demonstrated the cell death caused by salsolinol in human dopaminergic neuroblastoma SH-SY5Y cells to be apoptotic [18]. Apoptosis caused by this neurotoxin is thought to be mediated by an intracellular sequential process, loss of mitochondrial membrane potential, activation of caspases and DNA fragmentation [18,41].…”

Section: Discussionmentioning

confidence: 99%

“…So far, Naoi et al demonstrated the cell death caused by salsolinol in human dopaminergic neuroblastoma SH-SY5Y cells to be apoptotic [18]. Apoptosis caused by this neurotoxin is thought to be mediated by an intracellular sequential process, loss of mitochondrial membrane potential, activation of caspases and DNA fragmentation [18,41].…”

Section: Discussionmentioning

confidence: 99%

“…Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) might represent such a neurotoxic candidate. It can be easily endogenously synthesized from dopamine and acetaldehyde by salsolinol synthase or from dopamine and pyruvic acid or delivered exogenously [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Kurnik

Gil

Gajda

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Impairment of the enteric nervous system has been suggested to occur within the pathogenesis of neurodegenerative diseases. Thus, in the current study, we consider salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) as a substance that can potentially induce myenteric neurodegeneration. Material and methods. Male Wistar rats were subjected to continuous intraperitoneal dosing of salsolinol (200 mg/kg in total) with osmotic mini-pumps for either two or four weeks. An equivalent group of rats served as the control. Jejunal myenteric neurons were subjected to immunofluorescence staining to detect neuron specific protein -protein gene product (pan-neuronal marker, PGP 9.5), nitric oxide synthase (NOS), choline acetyltransferase (ChAT), Bax-protein and alpha-synuclein. In search of any functional impairment within the gastrointestinal tract, gut motility was assessed by determining the residual solid food contents in the stomach and the small and large intestine transit. Results. The myenteric neuron count, the mean size of the neuron body, the area of ganglia and the diameter of nerve strands were decreased in both of the salsolinol-treated groups compared with the controls. The number of NOS-positive cells was lower in the salsolinol-treated groups, while the number of ChAT-positive cells remained unchanged in comparison with the controls. Neurons expressing the pro-apoptotic Bax protein and alpha-synuclein deposits were observed among the myenteric neurons of the salsolinol-treated rats. Conclusions. Salsolinol evokes enteric neuronal cell death via initiation of apoptosis and leads to the formation of pathological aggregates of alpha-synuclein. Impairment of myenteric neurons, mainly the inhibitory motor neurons, might be responsible for the abnormal intestinal transit. Thus, salsolinol might be regarded as a suitable compound for inducing experimental enteric neurodegeneration in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Kurnik

Gil

Gajda

et al. 2015

Folia Histochem Cytobiol.

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“…A series of TIQ derivatives such as salsolinols, which exist in the mammalian brain and are structurally related to MPP + , are potent inhibitors of NADH ubiquinone reductase (complex I) in mitochondria and candidates of endogenous neurotoxins (1,2). Both TIQ and MPP + are reported to cause apoptosis in PC12 cells (7,8) and dopaminergic neurons (2,6,8,27).…”

Section: Discussionmentioning

confidence: 99%

“…A series of naturally occurring neurotoxic 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives such as salsolinols exist in the mammalian brain, and TIQ derivatives are candidates for endogenous parkinsonogenic compounds (1,2). The cell death caused by the TIQ derivatives in dopaminergic human neuroblastoma SH-SY5Y cells proved to be apoptotic (2).…”

Section: Introductionmentioning

confidence: 99%

Possible Role of Interleukin-6 in PC12 Cell Death Induced by MPP+ and Tetrahydroisoquinoline

et al. 2003

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Abstract. Interleukin (IL)-6 has been shown to protect neuronal cells from cell death induced by various stimulants. Although neuronal cells including PC12 cells were shown to produce IL-6, little is known about the effects of dopaminergic neurotoxins, 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-4-phenylpyridinium ion (MPP + ), on IL-6 expression in PC12 cells. In the present study, we investigated the role of IL-6 in the TIQ-and MPP + -induced cell death in PC12 cells. Treatment with 3.2 mM TIQ for 24 h caused a delayed cell death (lactate dehydrogenase (LDH) leakage and nuclear DNA fragmentation) markedly 72 h after the addition. Addition of 0.4 mM MPP + caused LDH leakage and nuclear DNA fragmentation 24 h after the addition. The cell death induced by MPP + was inhibited by an inhibitor of caspases, z-Val-Ala-Asp(OMe)-fluoromethylketone. The cell death induced by TIQ or MPP + was inhibited by nerve growth factor and 10% serum and significantly enhanced by the treatment with anti-IL-6 antibody. Both neurotoxins decreased the IL-6 mRNA level in PC12 cells without changing the other tested mRNA levels (IL-1a , b-actin, etc.). These findings suggest that dopaminergic neurotoxins cause cell death in PC12 cells at least partially by changing IL-6 expression.

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Resistance of the insect cell line IPLB‐LdFB to salsolinol‐induced apoptosis

Ottaviani

Nappi

Vass

2001

Arch Insect Biochem Physiol

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Apoptosis is a form of cell death that is manifested in Parkinson's disease (PD) and certain other neurodegenerative disorders. Metabolites of salsolinol (SAL), an intraneuronal, dopamine-derived tetrahydroisoquinoline (TIQ), have been shown to induce apoptosis in human dopaminergic neuroblastoma cells, implicating these molecules as causative or contributory factors in the selective killing of nigrostriatal dopaminergic neurons, a cardinal manifestation of Parkinson's disease. Since insects employ dopamine and related catecholamines in a variety of processes including cuticular sclerotization and cellular immune reactions, it was of interest to know how insect cells metabolized exogenous SAL. Propidium iodide staining combined with flow cytometry showed that IPLB-LdFB cells from Lymantria dispar exhibited no significant (P < 0.05) increase in apoptosis when incubated for 48 h with concentrations of SAL ranging from 10 microM to 1 mM. A significant increase in apoptosis (P < 0.05) was observed in cell cultures containing the highest concentration of SAL tested (5 mM), but only 12.4% of the cells manifested this form of cell death. High pressure liquid chromatography with electrochemical detection (HPLC-ED) was used to document the production of two potentially cytotoxic quinonoids generated during the autoxidation of SAL, a reaction that was found to be significantly (P < 0.05) enhanced by peroxidase. The resistance of IPLB-LdFB cells to SAL-induced apoptosis is attributed to the ability of these insect cells to metabolize and/or detoxify such dopamine-derived catecholic TIQs. Thus, the biochemical pathways employed by insect cells in these processes may be of considerable interest to individuals investigating certain neurodegenerative disorders.

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Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons

Cited by 54 publications

References 80 publications

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Possible Role of Interleukin-6 in PC12 Cell Death Induced by MPP+ and Tetrahydroisoquinoline

Resistance of the insect cell line IPLB‐LdFB to salsolinol‐induced apoptosis

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