Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture

Jayalakshmi, K.; Sairam, M.; Singh, Shashi Bala; Sharma, Shivani; Ilavazhagan, G.; Banerjee, P. K.

doi:10.1016/j.brainres.2005.03.054

Cited by 77 publications

(44 citation statements)

References 37 publications

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“…In the present study, we observed a decrease in ROS generation on administration of ferric ion chelator, DFO, during hypoxic exposure. Supplementation of NAC, known to improve neuronal survival in hypoxia by improving the synthesis of glutathione (primary antioxidant in the cells) (Jayalakshmi et al, 2005), resulted in decreased ferric ion deposition and reduced generation of ROS during hypoxia, indicating a correlation between the cellular antioxidant status, redox state of iron, and generation of free radicals. The NAC supplementation also maintained Ngb expression close to normoxic levels providing further evidence on the role of cellular antioxidant status on the stability of Ngb.…”

Section: Discussionmentioning

confidence: 99%

Neuroglobin Regulates Hypoxic Response of Neuronal Cells through Hif-1α- and Nrf2-mediated Mechanism

Hota

Srivastava

et al. 2012

J Cereb Blood Flow Metab

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Oxygen sensing in hypoxic neurons has been classically attributed to cytochrome c oxidase and prolyl-4-hydroxylases and involves stabilization of transcription factors, hypoxia-inducible factor-1a (Hif-1a) and nuclear factor erythroid 2-related factor 2 (Nrf2) that mediate survival responses. On the contrary, release of cytochrome c into the cytosol during hypoxic stress triggers apoptosis in neuronal cells. We, here advocate that the redox state of neuroglobin (Ngb) could regulate both Hif-1a and Nrf2 stabilization and cytochrome c release during hypoxia. The hippocampal regions showing higher expression of Ngb were less susceptible to global hypoxia-mediated neurodegeneration. During normoxia, Ngb maintained cytochrome c in the reduced state and prevented its release from mitochondria by using cellular antioxidants. Greater turnover of oxidized cytochrome c and increased utilization of cellular antioxidants during acute hypoxia altered cellular redox status and stabilized Hif-1a and Nrf2 through Ngb-mediated mechanism. Chronic hypoxia, however, resulted in oxidation and degradation of Ngb, accumulation of ferric ions and release of cytochrome c that triggered apoptosis. Administration of N-acetyl-cysteine during hypoxic conditions improved neuronal survival by preventing Ngb oxidation and degradation. Taken together, these results establish a role for Ngb in regulating both the survival and apoptotic mechanisms associated with hypoxia.

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Section: Discussionmentioning

confidence: 99%

Neuroglobin Regulates Hypoxic Response of Neuronal Cells through Hif-1α- and Nrf2-mediated Mechanism

Hota

Srivastava

et al. 2012

J Cereb Blood Flow Metab

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“…Primary neurons, especially the hippocampal neurons, are widely used for in vitro studies due to the relative simple nerve cell population and the expression of key neural phenotypic features as well as the involvement of the hippocampus in learning and memory [1][2][3][4]. In most of these studies, the primary neurons were cultured in culture dish or on glass slides with or without astrocytes [5].…”

Section: Introductionmentioning

confidence: 99%

Patch method for culture of primary hippocampal neurons

Tang

Severino

Iseppon

et al. 2017

Microelectronic Engineering

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In vitro culture of primary neurons, especially hippocampal neurons, is important for understanding cellular mechanisms in neurobiology. Actually, this is achieved by using culture dish or glass slide with surface coated proteins. Here, we proposed a patch method to culture primary neurons on a monolayer of gelatin nanofibers, electrospun and crosslinked on a microfabricated honeycomb frame of poly (ethylene glycol) diacrylate (PEGDA). By using such a patch method, neural networks could be formed with a minimal cell-exogenous materials contact and a maximal exposure of the cells to the medium. Interestingly, hippocampal cells, especially astrocytes, showed in-vivo like morphology and most of neurons were found in the porous areas inside the honeycomb compartments although the nanofibers were deposited everywhere of the frame. Finally, calcium imaging showed that primary neurons have a higher degree of neural activity on the patch than on glass.

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“…NAC has been tested as a promising antigenotoxic and anticarcinogenic agent in a variety of experiments [9][10][11], and is sold in pharmacies as a food supplement for such purposes. It has been proposed that the beneficial effect of NAC mainly comes from its capability of directly scavenging Å OH radicals as well as its function as a glutathione precursor [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

Yang

2006

FEBS Letters

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Reactive oxygen species, such as hydroxyl or superoxide radicals, can be generated by exogenous agents as well as from normal cellular metabolism. Those radicals are known to induce various lesions in DNA, including strand breaks and base modifications. These lesions have been implicated in a variety of diseases such as cancer, arteriosclerosis, arthritis, neurodegenerative disorders and others. To assess these oxidative DNA damages and to evaluate the effects of the antioxidant N-acetyl-L L-cysteine (NAC), atomic force microscopy (AFM) was used to image DNA molecules exposed to hydroxyl radicals generated via Fenton chemistry. AFM images showed that the circular DNA molecules became linear after incubation with hydroxyl radicals, indicating the development of double-strand breaks. The occurrence of the double-strand breaks was found to depend on the concentration of the hydroxyl radicals and the duration of the reaction. Under the conditions of the experiments, NAC was found to exacerbate the free radical-induced DNA damage.

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Neuroprotective effect of N-acetyl cysteine on hypoxia-induced oxidative stress in primary hippocampal culture

Cited by 77 publications

References 37 publications

Neuroglobin Regulates Hypoxic Response of Neuronal Cells through Hif-1α- and Nrf2-mediated Mechanism

Neuroglobin Regulates Hypoxic Response of Neuronal Cells through Hif-1α- and Nrf2-mediated Mechanism

Patch method for culture of primary hippocampal neurons

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

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