Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: Implications for parkinson’s disease

Copeland, Robert L.; Leggett, Yaminah A.; Kanaan, Yasmine; Taylor, Robert E.; Tizabi, Yousef

doi:10.1007/bf03033982

Cited by 41 publications

(38 citation statements)

References 22 publications

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“…Copeland et al sought to determine whether salsolinol-induced apoptosis could be prevented by nicotine. They pretreated the neuroblastoma cell line SH-SY5Y with 0.1 mM nicotine and then induced apoptosis with 0.8 mM salsolinol for 24 h. Their study revealed that nicotine pretreatment resulted in inhibition by more than 50% of salsolinol-induced cytotoxicity (p \ 0.01), which was blocked by mecamylamine, a non-selective nicotinic antagonist as well as conotoxins with selective antagonism against a3-containing nAChRs [25].…”

Section: Cells From the Neuronal Systemmentioning

confidence: 97%

Nicotine and apoptosis

Zeidler¹,

Albermann

Lang

2007

Apoptosis

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Cigarette smoking is associated with a plethora of different diseases. Nicotine is the addictive component of cigarette but also acts onto cells of the non-neuronal system, including immune effector cells. Although nicotine itself is usually not referred to as a carcinogen, there is ongoing debate whether nicotine functions as a 'tumor enhancer.' By binding to nicotinic acetylcholine receptors, nicotine deregulates essential biological processes like angiogenesis, apoptosis, and cell-mediated immunity. Apoptosis plays critical roles in a wide variety of physiologic processes during fetal development and in adult tissue and is also a fundamental aspect of the biology of malignant diseases. This review provides an overlook how nicotine influences apoptotic processes and is thus directly involved in the etiology of pathological conditions like cancer and obstructive diseases.

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Section: Cells From the Neuronal Systemmentioning

confidence: 97%

Nicotine and apoptosis

Zeidler¹,

Albermann

Lang

2007

Apoptosis

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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%

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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“…Different groups have investigated the effects of nicotine on apoptosis both in vitro and in vivo, and they have revealed a correlation between nicotine exposure and apoptosis. Several studies have reported that nicotine has a protective effect via inhibiting apoptosis [1,2,3,4,5,6,7], while others have shown the opposite [8,9,10,11,12]. Recent studies have shown that nicotine can increase oxidative stress, which may be associated with apoptosis [13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Nicotine Promotes Cardiomyocyte Apoptosis via Oxidative Stress and Altered Apoptosis-Related Gene Expression

et al. 2010

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Objective: To investigate the effect of nicotine on cardiomyocyte apoptosis in vitro and explore the potential mechanisms involved. Methods: The MTT assay was used to detect the viability of cultured cardiomyocytes exposed to different concentrations of nicotine (0.1–100 µM). Laser confocal microscopy, TUNEL assay and flow cytometry were utilized to detect cardiomyocyte apoptosis. Oxidative stress was evaluated by the levels of lactic dehydrogenase, malondialdehyde and superoxide dismutase in the supernatant of culture media. Real-time PCR was conducted to identify mRNA expression changes in apoptosis-related genes between the nicotine and the control group. Results: Nicotine was found to inhibit cardiomyocyte viability in a concentration-dependent manner. Our results demonstrated that nicotine can promote cardiomyocyte apoptosis and the antioxidant glutathione can protect cardiomyocytes from apoptosis via inhibition of nicotine-induced oxidative stress. Real-time PCR indicated that the expression of Bcl-2, Pax3, Bmp4 and Slug was down-regulated in the nicotine group, while the expression of P53, Bax and Msx1 was up-regulated. Conclusion: Nicotine promotes cardiomyocyte apoptosis by inducing oxidative stress and disrupting apoptosis-related gene expression.

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Neuroprotective effects of nicotine against salsolinol-induced cytotoxicity: Implications for parkinson’s disease

Cited by 41 publications

References 22 publications

Nicotine and apoptosis

Nicotine and apoptosis

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

Nicotine Promotes Cardiomyocyte Apoptosis via Oxidative Stress and Altered Apoptosis-Related Gene Expression

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