Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein

Wanpen, Sawitri; Govitrapong, Piyarat; Shaik, Shavali; Sangchot, Patcharee; Ebadi, Manuchair

doi:10.1016/j.brainres.2004.01.054

Cited by 58 publications

(41 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A possible explanation of the difference is that we used different toxic compounds, salsolinol and MPTP, in the two experiments. These two compounds both generate reactive oxygen species (ROS) as mediators of toxicity, 15,16) and both inhibit a-ketoglutarate dehydrogenase, 17) but MPTP inhibits complex I of the mitochondrial respiratory chain, while salsolinol inhibits complex II.…”

Section: Resultsmentioning

confidence: 99%

Parkinsonism-Preventing Activity of 1-Methyl-1,2,3,4-tetrahydroisoquinoline Derivatives in C57BL Mouse in Vivo

Okuda

Kotake

Ohta

2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of nigro-striatal dopaminergic neurons and reduction in the level of dopamine in this area. Since the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) could induce parkinsonism in humans, 1) 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives have been considered as candidate endogenous causative factors of idiopathic Parkinson's disease (PD), because of their structural similarity to MPTP. We have reported that tetrahydroisoquinoline derivatives (Fig. 1), such as TIQ, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ),2) 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), 3) and 1-(3Ј,4Ј-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3Ј,4ЈDHBnTIQ), 4) exist in the brain of mammalians of several species. While the content of 1BnTIQ tends to be increased in cerebrospinal fluid (CSF) of PD patients, 3) 1MeTIQ is significantly decreased in the parkinsonian brain and MPTP-injected mouse brain. 5,6) Bradykinesia, one of the symptoms of PD, was induced by injection of TIQ, 1BnTIQ, or 3Ј,4ЈDHBnTIQ in mice, 2,3) so these TIQ derivatives are considered to be parkinsonism-inducing substances. MPTP and TIQ derivatives have inhibitory activities towards complex I of the mitochondrial respiratory chain and tyrosine hydroxylase. 9) Thus, 1MeTIQ is a possible endogenous PD-preventing substance. Since 1MeTIQ is an endogenous amine, it may be synthesized enzymatically. Indeed, a candidate enzyme was partially purified from mitochondrial-synaptosomal fraction of rat brain, 10) and its regional distribution was examined in monkey brain.11) However, the mechanism of the parkinsonism-preventing activity of 1MeTIQ is still unknown.We have synthesized derivatives of 1MeTIQ ( Fig. 1) and evaluated their in vitro neurotoxicity and protective activity against toxicity due to salsolinol in SH-SY5Y human neuroblastoma cells.12) The introduction of one methoxyl group into 1MeTIQ increased the toxicity, especially in the case of 7-methoxy-1MeTIQ. The introduction of one hydroxyl group, however, reduced the toxicity. 1MeTIQ showed a week (not statistically significant) in vitro protective effect against the toxicity of salsolinol. 6-or 7-Hydroxy-1MeTIQ showed a greater (statistically significant) protective effect at 20 mM concentration against the toxicity of 20 or 40 mM salsolinol.In the present study, we examined whether these hydroxylsubstituted 1MeTIQ derivatives have parkinsonism-preventing activity in C57BL/6N mice by means of the pole test, and measured the brain dopamine content. MATERIALS AND METHODSReagents 1MeTIQ, 5-hydroxy-1MeTIQ, 6-hydroxy1MeTIQ and 7-hydroxy-1MeTIQ were synthesized according to the literature. 6,12,13) Treatment of the Reagents Twenty-four C57BL/6N male mice were divided into six groups (nϭ4) with the aid of a table of random numbers. Saline or a 1MeTIQ derivative Minami-ku, Hiroshima 734-8553, Japan. Received February 28, 2006; accepted April 17, 2006; published online April 21, 2006 1- Methyl-1,2,3,4-tetrah...

show abstract

Section: Resultsmentioning

confidence: 99%

Parkinsonism-Preventing Activity of 1-Methyl-1,2,3,4-tetrahydroisoquinoline Derivatives in C57BL Mouse in Vivo

Okuda

Kotake

Ohta

2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…In this investigation several neurotoxins were chosen as oxidative stressors. Salsolinol has been reported to cause oxidative stress by increasing ROS levels, decreasing ATP and glutathione levels in SH-SY5Y cell line by inhibiting mitochondrial complex-I and complex-II enzyme activities, tyrosine hydroxylase and monoamine oxidase [7,19,20]. Cell death was not inhibited by the addition of antioxidants such as -tocopherol or the water-soluble vitamin E analogue-Trolox C, however nicotine and donepezil restored cell survival, indicating that in the salsolinol toxicity nicotinic receptors could be involved [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular ROS generation can be induced by a number of diverse insults, e.g. salsolinol, 6-OHDA, 3-HK, Aβ, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-(MPTP) or rotenone [3][4][5][6][7]. Physiologically the only available defence against ROS in mitochondria are enzymes (for example superoxide dismutase, catalase, peroxidase) or low molecular weight oxidants (e.g.…”

Section: Introductionmentioning

confidence: 99%

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Wszelaki¹,

Melzig²

2013

View full text Add to dashboard Cite

Oxidative stress has been implicated as one of the causes in cell death in many neurodegenerative disorders. Due to antioxidative properties in vitro, the use of flavonoids and other polyphenolic compounds synthesised by plants are considered to be a promising strategy to prevent Alzheimer's disease and Parkinsons's disease. In the present study, we tested protective effects of some polyphenols and sodium pyruvate on 6-hydroxydopamine (6-OHDA), salsolinol and 3-hydroxykynurenine (3-HK) induced neurotoxicity in human neuroblastoma SH-SY5Y cells. We found that luteolin prevented from 6-OHDA and 3-HK induced cell viability reduction and that one of the mechanisms involved in the neuroprotective process was the ability to increase the level of cellular ATP. However, luteolin was ineffective against salsolinol-induced toxicity. Neither pre-treatment with flavonoids nor simultaneous addition had any protective effects on 6-OHDA, salsolinol or 3-HK induced neurotoxicity. Interestingly, both pre-treatment and co-treatment with pyruvate provided protection against 6-OHDA, salsolinol or 3-HK induced toxicity. Moreover, luteolin and sodium pyruvate, administered together, acted additively, so to achieve the same effect, lower concentrations were needed. The ability of luteolin and sodium pyruvate to reduce toxicity of 6-OHDA and 3-HK in SH-SY5Y cells may be related to two different neuroprotective mechanisms and the capability to penetrate into the cell.

show abstract

“…In particular, exposure to isoquinolines such as salsolinol, norsalsolinol and N-methyl-(R)-salsolinol in various cell lines induced apoptotic cell death due to oxidative stress such as increased ROS production (possibly mediated by copper) and oxidative DNA damage (Chun et al, 2001a;Jung & Surh, 2001;Kim et al, 2001;Kobayashi et al, 2009;Maruyama et al, 2002;Naoi et al, 2000;Storch et al, 2000;Wanpen et al, 2004;Yi et al, 2006a;Yi et al, 2006b). Aside from cell death and oxidative stress, other isoquinoline-induced key events potentially leading to PD pathogenesis have been mentioned.…”

Section: Isoquinolinesmentioning

confidence: 99%

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Choi¹,

Polcher²,

Joas³

2016

EFSA Supporting Publications

View full text Add to dashboard Cite

This report presents the outcomes of a systematic review (SR) identifying the mechanisms and chemicals involved in the pathogenesis of Parkinson's disease (PD) and childhood leukaemia (CL). This work serves as a basis for defining and mapping the causal linkages between a molecular initiating event (MIE) and a final adverse outcome (AO) that are relevant for the development of a prototype adverse outcome pathway (AOP) for assessing risk factors for PD and CL. Search for literature from 1990 to present was conducted using Web of Science, PubMed and TOXNET, and relevant references were selected using established inclusion/exclusion criteria and ranked using a set of quality control factors.For PD, 7,384 individual references were identified to be relevant for PD pathogenesis and chemicals associated with PD. Dopaminergic neurodegeneration in the substantia nigra leading to locomotor deficits was identified as the AO in PD. Other identified key events in PD pathogenesis include mitochondrial dysfunction, cellular accumulation of alpha-synuclein and oxidative stress. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and paraquat are some chemicals identified to be associated with PD pathogenesis.For CL, 1,988 individual references were identified to be relevant for CL pathogenesis and chemicals associated with CL. Chromosomal translocation, genetic damage/mutation and hyperdiploidy are considered as driving forces of CL. Except for infant leukaemia, CL pathogenesis requires a 'two-hit' model with an initiating event occurring in utero followed by a secondary hit potentially occurring after birth. Potential MIEs leading to these driving mechanisms include aberrant DNA topoisomerase II activity and erroneous DNA repair. Epigenetics appears to also play an influential role in CL pathogenesis. Benzene, bioflavonoids and organophosphates are some chemicals identified to be implicated in CL pathogenesis.The challenges of developing AOPs for these two diseases and the data gaps identified from the outcomes of this SR are also elaborated in this report. The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. KEY WORDSSystematic Review, Parkinson Disease, Childhood Leukaemia, Pathogenesis, Chemicals, Pesticides, Adverse Outcome Pathway SUMMARYThe aim of this project was to perform a systematic review (SR) to collect relevant publications related to the mechanisms involved in the pathogenesis of Parkinson's disease (PD)...

show abstract

Salsolinol, a dopamine-derived tetrahydroisoquinoline, induces cell death by causing oxidative stress in dopaminergic SH-SY5Y cells, and the said effect is attenuated by metallothionein

Cited by 58 publications

References 42 publications

Parkinsonism-Preventing Activity of 1-Methyl-1,2,3,4-tetrahydroisoquinoline Derivatives in C57BL Mouse in Vivo

Parkinsonism-Preventing Activity of 1-Methyl-1,2,3,4-tetrahydroisoquinoline Derivatives in C57BL Mouse in Vivo

Additive Protective Effects of Luteolin and Pyruvate against 6-Hydroxydopamine and 3-Hydroxykynurenine Induced Neurotoxicity in SH-SY5Y Cells

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

Contact Info

Product

Resources

About