Antiapoptotic effects of nicotine in its protection against salsolinol-induced cytotoxicity

Copeland, Robert L.; Das, Jharna R.; Kanaan, Yasmine; Taylor, Robert E.; Tizabi, Yousef

doi:10.1007/bf03033901

Cited by 36 publications

(44 citation statements)

References 20 publications

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“…Non-smokers develop Parkinson's Disease at twice the frequency of smokers [39][40][41]. Animal studies show that cigarette smoke protects against MPTP-induced neurotoxicity in the dopaminergic nigrostriatal system, possibly by protecting neurons against oxidative damage caused by the metabolism of dopamine [42][43][44]. Nicotine has been shown in neuronal cultures to offer protection against neurotransmitter-related excitotoxicity [45,46], and against arachadonic acid [47].…”

Section: Discussionmentioning

confidence: 97%

Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

et al. 2010

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Despite vasoactive properties, administration of NRT among active smokers with acute SAH appeared to be safe, with similar rates of vasospasm and DCI, and a slightly higher rate of seizures. The association of NRT with lower mortality could be due to chance, to uncontrolled factors, or to a neuroprotective effect of nicotine in active smokers hospitalized with SAH, and should be tested prospectively.

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Section: Discussionmentioning

confidence: 97%

Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

et al. 2010

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“…A previous study demonstrated that CIQs, such as salsolinol and NM-salsolinol are promising endogenous neurotoxins that may lead to the development of PD (19). Thus, a ̔vicious̓ cycle may be induced by CIQs.…”

Section: Discussionmentioning

confidence: 99%

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes

Song

Xin

Xie

et al. 2013

International Journal of Molecular Medicine

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Abstract. There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which areincreased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD. IntroductionDiabetes mellitus (DM), as a state of chronic hyperglycemia, and Parkinson's disease (PD) are diseases which consist a global health threat. In recent years, there have been increasing data indicating that hyperglycemia is associated with an increased risk of developing PD (1,2). However, the mechanisms underlying the association between hyperglycemia and PD have not yet been elucidated.Deng and Rajput (6) were the first to report, in 2001, that 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ), a salsolinol-like compound, is found at highly concentrated levels in the brains of patients who suffer from PD (3). When the brains of deceased patients with PD were compared to those of normal subjects, it was found that patients with PD presented elevated levels of ADTIQ in all the examined brain areas. This finding indicated that elevated ADTIQ expression levels may be one of the mechanisms involved in the increased risk patients with diabetes have of developing PD (4).Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycem...

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“…Cell viability was quantitatively determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay as described in detail previously (Copeland et al 2005(Copeland et al , 2007. Briefly, cells (1.5 9 10 4 cells per well) were plated in a 96-well plate in above media.…”

Section: Cell Viabilitymentioning

confidence: 99%

“…The observance of high levels of salsolinol in the cerebrospinal fluid of patients with PD has led to the suggestion that salsolinol might be involved in the etiology or loss of dopamine neurons in at least some Parkinson patients (Storch et al 2002;Maruyama et al 2004). A neuroprotective effect of nicotine against salsolinol-induced toxicity in immortal SH-SY5Y cells was recently reported (Copeland et al 2005(Copeland et al , 2007. SH-SY5Y cells, derived from human neuroblastoma cells are extensively used as a model to study nigral dopaminergic neurons as they express high level of dopaminergic activity (Storch et al 2002;Maruyama et al 2004;Naoi et al 2004).…”

Section: Introductionmentioning

confidence: 97%

“…Therefore, there is an urgent need for more effective and enduring medications. Although the etiology of PD remains elusive, various endogenous and exogenous toxicants may selectively damage the nigral dopaminergic neurons (Storch et al 2002;Maruyama et al 2004;Naoi et al 2004;Copeland et al 2007;Peng et al 2009). Availability of these compounds and cell lines that represent dopamine containing neurons has tremendously facilitated the search for degenerative mechanisms as well as possible novel pharmacotherapy in PD.…”

Section: Introductionmentioning

confidence: 99%

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Additive Protective Effects of Donepezil and Nicotine Against Salsolinol-Induced Cytotoxicity in SH-SY5Y Cells

Das

Tizabi

2009

Neurotox Res

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Although the etiology of Parkinson's disease (PD) remains elusive, a number of toxins including elevated salsolinol, an endogenous metabolite of dopamine may contribute to its pathology. It was reported recently that nicotine may have protective effects against salsolinol-induced toxicity in human neuroblastoma derived SH-SY5Y cells and that these effects of nicotine are mediated by nicotinic receptors. Donepezil (Aricept) is a reversible non-competitive acetylcholinesterase inhibitor that is approved for use in mild to moderate Alzheimer's disease. The increase in acetylcholine concentrations is believed to be the major contributory factor in donepezil's therapeutic efficacy. However, cholinesterase inhibitors may also directly interact with nicotinic receptors and possess neuroprotective properties. In this study, we sought to determine whether donepezil may have protective effects against salsolinol-induced toxicity in SH-SY5Y cells and whether the combination of donepezil and nicotine may result in additive protection. Moreover, it was of interest to elucidate the role of nicotinic receptors as well as cell cycle and apoptosis in mechanism of action of these compounds. SH-SY5Y cells were exposed to 0.6 mM salsolinol with and without various drug pretreatments for 48 h. Nicotine (50 muM) resulted in approximately 54% protection and donepezil (5 muM) resulted in approximately 40% protection, and the combination of the two resulted in an additive (approximately 93%) protection against salsolinol-induced toxicity. Salsolinol caused an arrest of the cells in G(1)-phase of cell cycle and an increase in apoptotic indices that were blocked by the combination of donepezil and nicotine. Mecamylamine, a non-selective nicotinic receptor antagonist completely blocked the effects of nicotine and partially attenuated the effects of donepezil. A combination of atropine, a muscarinic receptor antagonist and mecamylamine completely blocked the effects of donepezil, indicating involvement of both nicotinic and muscarinic receptors in donepezil's actions. The findings suggest a therapeutic potential for the combination of donepezil and nicotine in PD.

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Antiapoptotic effects of nicotine in its protection against salsolinol-induced cytotoxicity

Cited by 36 publications

References 20 publications

Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

Transdermal Nicotine Replacement Therapy in Cigarette Smokers with Acute Subarachnoid Hemorrhage

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes

Additive Protective Effects of Donepezil and Nicotine Against Salsolinol-Induced Cytotoxicity in SH-SY5Y Cells

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