Differential protection of pre- versus post-treatment with curcumin, Trolox, and N -acetylcysteine against acrylonitrile-induced cytotoxicity in primary rat astrocytes

Bai, Yu; Yin, Chang-Cheng; Zhao, Wei; Li, Ben; Qian, Hai; Ma, Jing; Xing, Guangwei; Wang, Shuhua; Li, Fang; Aschner, Michael; Lu, Rongzhu

doi:10.1016/j.neuro.2015.09.011

Cited by 18 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primary neonatal rat astrocytes were prepared as previously described (Bai et al 2015(Bai et al , 2016Fang et al 2016;Yang et al 2018;Yin et al 2011). The procedures were as follows: Rats were rapidly decapitated, and the cerebral hemispheres were quickly obtained and rinsed with 4°C phosphate buffered solution (PBS).…”

Section: Primary Rat Astrocyte Isolation and Culturementioning

confidence: 99%

“…We investigated whether ROS production were associated with decreased HIF-1a expression in MeHg-exposed astrocytes. Astrocytes were pretreated with NAC (2:5 mM, 4 h) and Trolox (2:5 mM, 4 h) followed by 10 lM MeHg for 0:5 h. NAC and Trolox are antioxidants that are commonly used to mitigate ROS (Aremu et al 2008;Bai et al 2015;Kaur et al 2010). As shown in Figures 5A and 5C, cells pretreated with either NAC or Trolox and then treated with MeHg exhibited higher HIF-1a protein levels, similar to those of control cells, than those treated with MeHg alone.…”

Section: Hif-1a Protein Expression and Cell Proliferation After Pretrmentioning

confidence: 99%

See 1 more Smart Citation

Acute Methylmercury Exposure and the Hypoxia-Inducible Factor-1α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro

Chang

Yang

Zhou

et al. 2019

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

BACKGROUND: As a ubiquitous environmental pollutant, methylmercury (MeHg) induces toxic effects in the nervous system, one of its main targets. However, the exact mechanisms of its neurotoxicity have not been fully elucidated. Hypoxia-inducible factor-1a (HIF-1a), a transcription factor, plays a crucial role in adaptive and cytoprotective responses in cells and is involved in cell survival, proliferation, apoptosis, inflammation, angiogenesis, glucose metabolism, erythropoiesis, and other physiological activities. OBJECTIVES: The aim of this study was to explore the role of HIF-1a in response to acute MeHg exposure in rat brain and primary cultured astrocytes to improve understanding of the mechanisms of MeHg-induced neurotoxicity and the development of effective neuroprotective strategies. METHODS: Primary rat astrocytes were treated with MeHg (0-10 lM) for 0:5 h. Cell proliferation and cytotoxicity were assessed with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) release assay, respectively. Reactive oxygen species (ROS) levels were analyzed to assess the level of oxidative stress using 2 0 ,7 0-dichlorofluorescin diacetate (DCFH-DA) fluorescence. HIF-1a, and its downstream proteins, glucose transporter 1 (GLUT-1), erythropoietin (EPO), and vascular endothelial growth factor A (VEGF-A) were analyzed by means of Western blotting. Real-time PCR was used to detect the expression of HIF-1a mRNA. Pretreatment with protein synthesis inhibitor (CHX), proteasome inhibitor (MG132), or proline hydroxylase inhibitor (DHB) were applied to explore the possible mechanisms of HIF-1a inhibition by MeHg. To investigate the role of HIF-1a in MeHg-induced neurotoxicity, cobalt chloride (CoCl 2), 2-methoxyestradiol (2-MeOE2), small interfering RNA (siRNA) transfection and adenovirus overexpression were used. Pretreatment with N-acetyl-L-cysteine (NAC) and vitamin E (Trolox) were used to investigate the putative role of oxidative stress in MeHg-induced alterations in HIF-1a levels. The expression of HIF-1a and related downstream proteins was detected in adult rat brain exposed to MeHg (0-10 mg=kg) for 0:5 h in vivo. RESULTS: MeHg caused lower cell proliferation and higher cytotoxicity in primary rat astrocytes in a time-and concentration-dependent manner. In comparison with the control cells, exposure to 10 lM MeHg for 0:5 h significantly inhibited the expression of astrocytic HIF-1a, and the downstream genes GLUT-1, EPO, and VEGF-A (p < 0:05), in the absence of a significant decrease in HIF-1a mRNA levels. When protein synthesis was inhibited by CHX, MeHg promoted the degradation rate of HIF-1a. MG132 and DHB significantly blocked the MeHg-induced decrease in HIF-1a expression (p < 0:05). Overexpression of HIF-1a significantly attenuated the decline in MeHg-induced cell proliferation, whereas the inhibition of HIF-1a significantly increased the decline in cell proliferation (p < 0:05). NAC and Trolox, two established antioxidants, reversed the MeHg-induced decl...

show abstract

Section: Primary Rat Astrocyte Isolation and Culturementioning

confidence: 99%

Section: Hif-1a Protein Expression and Cell Proliferation After Pretrmentioning

confidence: 99%

Acute Methylmercury Exposure and the Hypoxia-Inducible Factor-1α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro

Chang

Yang

Zhou

et al. 2019

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

show abstract

“…The anti-inflammatory effect of curcumin is well-documented as one of main features of this natural non-toxic compound (Gullo et al, 2017). Thus, the detrimental effect of astrogliosis could be prevented with natural polyphenol compounds, especially curcumin (Yu et al, 2015). One more of the most important function of astrocytes is their involvement in blood-brain barrier (BBB) formation, integrity and remodeling.…”

Section: Discussionmentioning

confidence: 99%

Soluble curcumin prevents cadmium cytotoxicity in primary rat astrocytes by improving a lack of GFAP and glucose-6-phosphate-dehydrogenase

Nedzvetsky

Sukharenko

Kyrychenko

et al. 2018

Regul. Mech. Biosyst.

View full text Add to dashboard Cite

Cadmium (Cd) is a heavy metal which is widespread in various environmental components. Moreover several occupational diseases have the complications that are related to Cd cytotoxicity. Low doses of Cd exposure could induce pathogenetic disturbances in several sensitive cells as result of its long biological half-life and accumulation in vital tissue types. Prolonged Cd exposure was determined as main factor in accumulation of this metal ion over time in the liver, kidneys and neural tissue cells. The neurotoxic effect of Cd was presented in several articles which reported both in vivo and in vitro study. One of the main causes of Cd neurotoxicity is the ability of this ion to increase the permeability of the blood brain barrier. Despite a focus of attention on Cd cytotoxicity over the last few decades, the effect of Cd in neural tissue cells has been presented in a limited number of articles. The neurotoxic effect of Cd is accompanied by biochemical changes as well as a lack of functional activity of the central nervous system. Taking into account that the cytotoxic effect of Cd is associated with oxidative stress, inflammation and selective cell death, antioxidants could be used to protect neural tissue cells against both chronic and acute Cd exposure. Antioxidants protect diverse cell types against metal induced cytotoxicity. Curcumin is a natural polyphenol which exhibits antioxidant and anti-inflammatory effect. Soluble forms of cucrcumin can penetrate the blood brain barrier and protect neural tissue cells against detrimental effects of cytotoxic compounds. Glial cells are the most numerous cell population in CNS. Astrocytes possess the ability to protect the neuronal cells against cytotoxicity and maintain CNS functions. The cytoskeleton of astrocytes is constructed with glial fibrillary acidic protein (GFAP). GFAP is involved in essential functions of astrocytes and reflects astrocyte reactivity. The molecular mechanisms of the neurotoxic effect of Cd on glial cytoskeleton remain unknown. Primary astrocyte cell culture was used as model to assess the gliotoxic effect of Cd as well as the potency of low doses of soluble curcumin to ameliorate the neurotoxic effect of Cd. The obtained results demonstrated depletion of GFAP and glucose-6-phosphate-dehydrogenase (G6PD) in astrocytes treated with 10 µM Cd. The exposure to 5 µM curcumin ameliorated the expression both of GFAP and G6PD in Cd suppressed astrocytes. Moreover, low doses of soluble curcumin significantly prevented the detrimental effects of Cd on cell viability and indices of oxidative stress. The obtained results are evidence that soluble forms of curcumin improve astrocyte viability, cytoskeleton depletion and glucose utilization pathway. Thus, soluble curcumin possesses a neuroprotective effect directed on astrocyte cytoskeleton and metabolic energy production.

show abstract

“…Postnatal 1-to 2-day Sprague-Dawley (SD) rats were provided by the Laboratory Animal Center of the First Affiliated Hospital of Wenzhou Medical University. Primary astrocytes were prepared from the cerebral cortices of SD rats as described previously (Yin et al, 2011;Yu et al, 2015;Yuntao et al, 2016). Briefly, cerebral cortices were freed of meninges by microscope, minced, dissociated with 0.125% trypsin (Gibco, Grand Island, USA) for 15 min, passed through sterile nylon sieves, and placed in Dulbecco's modified Eagle's medium (DMEM; Gibco, Grand Island, USA) with 10% fetal bovine serum (FBS; Gibco, Grand Island, USA) and 1% penicillin/streptomycin (Gibco, Grand Island, USA).…”

Section: Primary Astrocyte Culture and Treatmentmentioning

confidence: 99%

Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy

Jin

Chen

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Objective: Hepatic encephalopathy (HE) characterized by neuropsychiatric abnormalities is a major complication of cirrhosis with high mortality. However, the pathogenesis of HE has not been fully elucidated. This study aimed to determine endogenous hydrogen sulfide (H 2 S) in the blood of HE patients and investigate the role of H 2 S in an astrocytic model of HE. Methods: Patients with and without HE were recruited to determine plasma H 2 S levels and blood microbial 16S rRNA gene. Rat astrocytes were employed as a model of HE by treatment of NH 4 Cl. Exogenous H 2 S was preadded. Cell viability was measured by Cell Counting Kit-8 (CCK-8) assay, and cell death was evaluated by lactate dehydrogenase (LDH) release. Apoptosis was determined by Hoechst 33342/Propidium Iodide (PI) Double Staining and Western blot analysis of apoptosis-related protein expression. Intracellular reactive oxygen species (ROS) levels were assessed by flow cytometer. Expressions of Nrf2 and its downstream regulated genes were examined by immunofluorescence staining and Western blot, respectively. Nrf2 gene knockdown was performed by antisense shRNA of Nrf2 gene. Results: There was a significant decrease in H 2 S levels in cirrhotic patients with HE compared with without HE. Blood microbiota analyses revealed that certain strains associated with H 2 S production were negatively correlated with HE. In vitro, H 2 S markedly attenuated NH 4 Cl-induced cytotoxicity, oxidative stress, and apoptosis. This effect was mediated by Nrf2/ARE signaling, and knockdown of Nrf2 expression abolished the antagonistic effect of H 2 S on NH 4 Cl-induced neurotoxicity in astrocytes. Conclusion: Levels of H 2 S and bacteria associated with H 2 S production are decreased in HE, and H 2 S functions as the neuroprotector against NH 4 Cl-induced HE by activating Nrf2/ARE signaling of astrocytes.

show abstract

Differential protection of pre- versus post-treatment with curcumin, Trolox, and N -acetylcysteine against acrylonitrile-induced cytotoxicity in primary rat astrocytes

Cited by 18 publications

References 55 publications

Acute Methylmercury Exposure and the Hypoxia-Inducible Factor-1α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro

Acute Methylmercury Exposure and the Hypoxia-Inducible Factor-1α Signaling Pathway under Normoxic Conditions in the Rat Brain and Astrocytes in Vitro

Soluble curcumin prevents cadmium cytotoxicity in primary rat astrocytes by improving a lack of GFAP and glucose-6-phosphate-dehydrogenase

Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy

Contact Info

Product

Resources

About