N-acetylcysteineamide protects against manganese-induced toxicity in SHSY5Y cell line
| Autor: | Shakila Tobwala, Yasaswi Maddirala, Nuran Ercal |
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| Rok vydání: | 2015 |
| Předmět: |
Time Factors
Antioxidant Cell Survival medicine.medical_treatment Glutathione reductase Biology medicine.disease_cause Antioxidants Lipid peroxidation Neuroblastoma chemistry.chemical_compound Adenosine Triphosphate Cell Line Tumor Malondialdehyde Manganism medicine Humans Drug Interactions Molecular Biology chemistry.chemical_classification Glutathione Peroxidase Manganese Dose-Response Relationship Drug General Neuroscience Glutathione peroxidase Glutathione medicine.disease Acetylcysteine Oxidative Stress Glutathione Reductase Biochemistry chemistry Lipid Peroxidation Neurology (clinical) Reactive Oxygen Species Oxidative stress Developmental Biology |
| Zdroj: | Brain Research. 1608:157-166 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2015.02.006 |
| Popis: | Manganese (Mn) is an essential trace element required for normal cellular functioning. However, overexposure of Mn can be neurotoxic resulting in the development of manganism, a syndrome that resembles Parkinson׳s disease. Although the pathogenetic basis of this disorder is unclear, several studies indicate that it is mainly associated with oxidative stress and mitochondrial energy failure. Therefore, this study is focused on (1) investigating the oxidative effects of Mn on neuroblastoma cells (SHSY5Y) and (2) elucidating whether a novel thiol antioxidant, N-acetylcysteineamide (NACA), provides any protection against Mn-induced neurotoxicity. Reactive oxygen species (ROS) were highly elevated after the exposure, indicating that mechanisms that induce oxidative stress were involved. Measures of oxidative stress parameters, such as glutathione (GSH), malondialdehyde (MDA), and activities of glutathione reductase (GR) and glutathione peroxidase (GPx) were altered in the Mn-treated groups. Loss of mitochondrial membrane potential, as assessed by flow cytometry and decreased levels of ATP, indicated that cytotoxicity was mediated through mitochondrial dysfunction. However, pretreatment with NACA protected against Mn-induced toxicity by inhibiting lipid peroxidation, scavenging ROS, and preserving intracellular GSH and mitochondrial membrane potential. NACA can potentially be developed into a promising therapeutic option for Mn-induced neurotoxicity. This article is part of a Special Issue entitled SI: Metals in neurodegeneration. |
| Databáze: | OpenAIRE |
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