Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

Silva-Palacios, Alejandro; Colín-González, Ana Laura; López-Cervantes, Stefanie Paola; Zazueta, Cecilia; Luna–López, Armando; Santamarı́a, Abel; Königsberg, Mina

doi:10.1016/j.redox.2017.03.029

Cited by 27 publications

(22 citation statements)

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“…One candidate pathway that may be targeted by drugs is the NRF-2 stress response. In brain tissue, astrocytes are the major cell type to activate this pathway [ 21 , 56 ], and this response may be triggered by pharmacological or non-pharmacological pre-conditioning strategies [ 57 , 58 ]. Stimulation or overexpression of NRF-2 in astrocytes leads to an intracellular GSH increase, to GSH release into the medium and to augmented protection of co-cultured neurons [ 21 , 40 , 41 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Prevention of neuronal apoptosis by astrocytes through thiol-mediated stress response modulation and accelerated recovery from proteotoxic stress

et al. 2018

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The development of drugs directly interfering with neurodegeneration has proven to be astonishingly difficult. Alternative therapeutic approaches could result from a better understanding of the supportive function of glial cells for stressed neurons. Therefore, here, we investigated the mechanisms involved in the endogenous neuro-defensive activity of astrocytes. A well-established model of postmitotic human dopaminergic neurons (LUHMES cells) was used in the absence ('LUHMES' mono-culture) or presence ('co-culture') of astrocytes. Inhibition of the LUHMES proteasome led to proteotoxic (protein aggregates; ATF-4 induction) and oxidative (GSH-depletion; NRF-2 induction) stress, followed by neuronal apoptosis. The presence of astrocytes attenuated the neuronal stress response, and drastically reduced neurodegeneration. A similar difference between LUHMES mono- and co-cultures was observed, when proteotoxic and oxidative stress was triggered indirectly by inhibitors of mitochondrial function (rotenone, MPP+). Human and murine astrocytes continuously released glutathione (GSH) into the medium, and transfer of glia-conditioned medium was sufficient to rescue LUHMES, unless it was depleted for GSH. Also, direct addition of GSH to LUHMES rescued the neurons from inhibition of the proteasome. Both astrocytes and GSH blunted the neuronal ATF-4 response and similarly upregulated NRF-1/NFE2L1, a transcription factor counter-regulating neuronal proteotoxic stress. Astrocyte co-culture also helped to recover the neurons’ ability to degrade aggregated poly-ubiquitinated proteins. Overexpression of NRF-1 attenuated the toxicity of proteasome inhibition, while knockdown increased toxicity. Thus, astrocytic thiol supply increased neuronal resilience to various proteotoxic stressors by simultaneously attenuating cell death-related stress responses, and enhancing the recovery from proteotoxic stress through upregulation of NRF-1.

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Section: Discussionmentioning

confidence: 99%

Prevention of neuronal apoptosis by astrocytes through thiol-mediated stress response modulation and accelerated recovery from proteotoxic stress

et al. 2018

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“…Triterpenoids and dimethyl fumarate are protective in genetic models of Huntington’s disease, improving survival and motor function and increasing striatal neuron survival [ 212 , 213 ], and curcumin is effective in multiple models of Huntington’s disease [ 214 , 215 , 216 ]. Dimethyl fumarate, CDDO-methylamide, sulforaphane, curcumin nanoparticles, tert-butylhydroquinone, the citrus flavonone naringin, the ginseng extract protopanaxtriol, the organic disulphide cystamine and AI-3 are all protective against 3-nitropropionic acid and decrease striatal lesion size in rats and mice [ 25 , 70 , 207 , 208 , 209 , 211 , 217 , 218 ]. Deletion of Nrf2 abolishes the protective effects of cystamine and tert-butylhydroquinone, confirming the role of Nrf2 in these effects [ 25 , 211 ].…”

Section: Huntington’s Diseasementioning

confidence: 99%

Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?

2017

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes. However, Nrf2 activity can be observed in neurons in post-mortem brain tissue and animal models of disease. Thus this interpretation may be false, and a detailed analysis of the cell type expression of Nrf2 in neurodegenerative diseases is required. This review describes the evidence for Nrf2 activation in each cell type in prominent neurodegenerative diseases and normal aging in human brain and animal models of neurodegeneration, the response to pharmacological and genetic modulation of Nrf2, and clinical trials involving Nrf2-modifying drugs.

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“…3-Nitropropionic acid (3-NPA) irreversibly inhibits the activity of succinate dehydrogenase and promotes ROS formation, thereby inducing oxidative stress [ 13 , 19 ]. Several studies have suggested that 3-NPA significantly increases ROS production in granulosa cells and ovaries and then induces ovarian oxidative damage in mammals [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of 3-nitropropionic acid inducing oxidative stress and apoptosis of granulosa cells in geese

Kang

Wang

et al. 2018

Bioscience Reports

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The mechanism of action by which oxidative stress induces granulosa cell apoptosis, which plays a vital role in initiating follicular atresia, is not well understood. In the present study, the effect of 3-nitropropionic acid (3-NPA) on oxidative stress and apoptosis in granulosa cells in geese was investigated. Our results showed that treatment with 3-NPA at 5.0 mmol/l for 24 h increased intracellular reactive oxygen species (ROS) production by 25.4% and decreased granulosa cell viability by 45.5% (P<0.05). Catalase and glutathione peroxidase gene expression levels in granulosa cells treated with 3-NPA were 1.32- and 0.49-fold compared with those of the control cells, respectively (P <0.05). A significant decrease in the expression level of B-cell lymphoma 2 (Bcl-2) protein and remarkable increases in the levels of Bax, p53 and cleaved-Caspase 3 proteins and the ratio of Bax/Bcl-2 expression in granulosa cells treated with 3-NPA were observed (P<0.05). Furthermore, a 38.43% increase in the percentage of early apoptotic cells was also observed in granulosa cells treated with 3-NPA (P<0.05). Moreover, the expression levels of NF-κB, Nrf2, Fhc, Hspa2 and Ho-1 in granulosa cells treated with 3-NPA were elevated 4.36-, 1.63-, 3.62-, 27.54- and 10.48-fold compared with those of the control cells (P<0.05), respectively. In conclusion, the present study demonstrates that treatment with 3-NPA induces ROS production and apoptosis and inhibits the viability of granulosa cells in geese. Furthermore, 3-NPA triggers increases in the expression of cleaved-Caspase 3 protein and the ratio of Bax/Bcl-2 expression, and induces the early apoptosis of granulosa cells.

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Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

Cited by 27 publications

References 89 publications

Prevention of neuronal apoptosis by astrocytes through thiol-mediated stress response modulation and accelerated recovery from proteotoxic stress

Prevention of neuronal apoptosis by astrocytes through thiol-mediated stress response modulation and accelerated recovery from proteotoxic stress

Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?

Effect of 3-nitropropionic acid inducing oxidative stress and apoptosis of granulosa cells in geese

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