Acute Cytotoxic Effects of Mercuric Compounds in Cultured Astrocytes Prepared from Cerebral Hemisphere and Cerebellum of Newborn Rats

Adachi, Tatsumi; Kunimoto, Manabu

doi:10.1248/bpb.28.2308

Cited by 9 publications

(7 citation statements)

References 22 publications

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“…This interaction decreases the levels of GSH and the oxidized glutathione ration (GSH/GSSG), which contributes to the occurrence of oxidative stress and cerebral cortex injury [35]. Other studies revealed that the GSH content is higher in cerebral cells than other different regions cells in the CNS [36, 37]. This may be the reason for the excessive accumulation of MeHg in cerebral cortex.…”

Section: Discussionmentioning

confidence: 99%

Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

Deng

Liu

et al. 2012

Oxidative Medicine and Cellular Longevity

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Objective. This study was to evaluate the effect of riluzole on methylmercury- (MeHg-) induced oxidative stress, through promotion of glutathione (GSH) synthesis by activating of glutamate transporters (GluTs) in rat cerebral cortex. Methods. Eighty rats were randomly assigned to four groups, control group, riluzole alone group, MeHg alone group, and riluzole + MeHg group. The neurotoxicity of MeHg was observed by measuring mercury (Hg) absorption, pathological changes, and cell apoptosis of cortex. Oxidative stress was evaluated via determining reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDAs), carbonyl, sulfydryl, and GSH in cortex. Glutamate (Glu) transport was studied by measuring Glu, glutamine (Gln), mRNA, and protein of glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1). Result. (1) MeHg induced Hg accumulation, pathological injury, and apoptosis of cortex; (2) MeHg increased ROS, 8-OHdG, MDA, and carbonyl, and inhibited sulfydryl and GSH; (3) MeHg elevated Glu, decreased Gln, and downregulated GLAST and GLT-1 mRNA expression and protein levels; (4) riluzole antagonized MeHg-induced downregulation of GLAST and GLT-1 function and expression, GSH depletion, oxidative stress, pathological injury, and apoptosis obviously. Conclusion. Data indicate that MeHg administration induced oxidative stress in cortex and that riluzole could antagonize this situation through elevation of GSH synthesis by activating of GluTs.

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Section: Discussionmentioning

confidence: 99%

Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

Deng

Liu

et al. 2012

Oxidative Medicine and Cellular Longevity

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“…5) A large portion of previous studies conducted on MeHg neurotoxicity have focused on astrocytes and neurons. 2,6,7) With regard to endothelial cells, the inhibitory effect of MeHg on the migration and tube formation of cultured human umbilical vein endothelial cells has been reported. 8) However, little is known regarding the effects of MeHg on vascular endothelial cell functions.…”

Section: Introductionmentioning

confidence: 99%

Methylmercury Retards the Repair of Wounded Monolayer of Human Brain Microvascular Endothelial Cells by Inhibiting Their Proliferation without Nonspecific Cell Damage

Hirooka

Fujiwara

Yamamoto

et al. 2007

JOURNAL OF HEALTH SCIENCE

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Methylmercury (MeHg) is an environmental pollutant that causes severe neuropathy in the brain of exposed humans and animals. It is possible that MeHg induces functional damage of the brain microvessels and neuropathy occurs secondarily. Thus, the effects of MeHg on the maintenance of vascular endothelial cell monolayer were investigated using a culture system of human brain microvascular endothelial cells. MeHg did not damage the morphology of the monolayer; however, it retarded the repair of the wounded monolayer. The proliferation of endothelial cells was observed to be inhibited by MeHg when assessed by the cell number, [3 H]thymidine incorporation, and lactate dehydrogenase (LDH) leakage in sparsely growing cells. Cadmium also decreased the [ 3 H]thymidine incorporation but failed to decrease the cell number; inorganic mercury and lead did not exhibit any inhibitory effect under the same conditions. Considering these results together, it is suggested that MeHg exhibits toxicity in the brain microvessels when the endothelial monolayer is damaged. MeHg specifically inhibits the proliferation of endothelial cells during the repair process of the damaged monolayers. The present data support the hypothesis that the mechanism of MeHg-induced neuropathy in the brain includes changes in the microenvironment of the neurons caused by functional damage to the microvessels.

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“…Animals Wistar rats obtained from CLEA Japan Co. (Tokyo, Japan) were maintained at 22.5 ± 2.5°C and 55 ± 10% relative humidity under a 12-h light/dark cycle, and were given standard laboratory chow and tap water ad libitum. Pregnant rats were prepared as previously described, 10,18) and housed individually until birth. The protocol for animal experiments was approved by the animal experimentation committee of Chiba Institute of Science.…”

Section: Methodsmentioning

confidence: 99%

“…12) Astrocytes were plated on poly-L-lysine (PLL; Sigma, St. Louis, MO, USA)coated culture plates (BD Bioscience, Billerica, MA, USA) or dishes (BD Bioscience), and maintained with 15% fetal calf serum (FCS; Invitrogen Co., Carlsbad, CA, USA)-containing medium (FCScM), the composition of which was previously described. [10][11][12] Cells on 24-well or 6-well plates or 10 cm dishes were used for the experiment using inhibitors or for determining expression levels of total or active RhoA, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…We have examined the influence of mercury compounds including MeHg on cell death and morphology in cultured astrocytes under several culture conditions. Susceptibility to cell death from MeHg is similar in the cerebral hemisphere and in cerebellar astrocytes, 10) whereas a region-dependent difference is observed in morphological change induced by MeHg exposure at 3 μM in astrocytes maintained in a serum-free defined medium (SFDM) containing 0.5 mM dibutyryl cyclic AMP (dbcAMP). 11) In cerebral hemisphere astrocytes, the morphology of almost all astrocytes changed from stellate to polygonal within 3 h after MeHg exposure at more than 2 μM.…”

Section: Introductionmentioning

confidence: 99%

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Acute Cytotoxic Effects of Mercuric Compounds in Cultured Astrocytes Prepared from Cerebral Hemisphere and Cerebellum of Newborn Rats

Cited by 9 publications

References 22 publications

Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

Riluzole-Triggered GSH Synthesis via Activation of Glutamate Transporters to Antagonize Methylmercury-Induced Oxidative Stress in Rat Cerebral Cortex

Methylmercury Retards the Repair of Wounded Monolayer of Human Brain Microvascular Endothelial Cells by Inhibiting Their Proliferation without Nonspecific Cell Damage

Involvement of Rho in Methylmercury-Induced Morphological Change in Cultured Astrocytes Obtained from Rat Cerebral Hemisphere

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