Antioxidants J811 and 17?-estradiol protect cerebellar granule cells from methylmercury-induced apoptotic cell death

Daré, Elisabetta; Götz, Mario E.; Zhivotovsky, Boris; Manzo, Luigi; Ceccatelli, Sandra

doi:10.1002/1097-4547(20001115)62:4<557::aid-jnr10>3.0.co;2-9

Cited by 85 publications

(56 citation statements)

References 44 publications

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“…On day 7, cell viability was analyzed by evaluating living cell permeability to impermeant DNA dies. Cells then were exposed for 24 h to 25 M H 2 O 2, 1 M MeHg, or 1 M colchicine, stimuli inducing chromatin condensation and appearance of high molecular weight DNA fragments (12)(13)(14)(15)(16). For biochemical analyses on unexposed cells, CGC were collected after 1 week in culture.…”

Section: Methodscontrasting

confidence: 58%

“…Cerebellar granule cells (CGC) prepared from 1-week-old rats exposed in utero to the synthetic glucocorticoid dexamethasone, which is poorly metabolized by 11 ␤-hydroxysteroid dehydrogenase, were exposed to stimuli that mimic conditions occurring in neurodegeneration and that we have previously shown to induce apoptosis in CGC (12)(13)(14)(15)(16). H 2 O 2 and methylmercury(MeHg) were used to induce oxidative stress, which is known to be involved in age-related disorders and the pathogenesis of a variety of neurological and neurodegenerative conditions, such as Alzheimer's disease (17), Parkinson's disease (18) and amyotrophic lateral sclerosis (19).…”

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confidence: 99%

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Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death

Ahlbom

Gogvadze

Chen

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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There is growing concern that prenatal exposure to excessive glucocorticoids may have deleterious effects on the development of various organs, including the nervous system. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids might produce long-term effects on neuronal cell survival. Pregnant rats were injected i.p. with 0.1 mg͞kg dexamethasone (DEX) from day 14 postconception, and cerebellar granule cells (CGC) were prepared from 1-week-old rats from DEX-treated and control dams. After 7 days in culture, cells were exposed to H 2O2, methylmercury, or colchicine at concentrations known to induce apoptotic cell death. After exposure to H 2O2 or methylmercury, both inducing oxidative stress, the number of apoptotic cells was significantly higher in DEX-than in control-CGC. Because mitochondria play a key role in apoptosis, mitochondrial function was investigated, and a decrease in the threshold level of Ca 2؉ necessary for induction of mitochondrial permeability transition, in Ca 2؉ accumulation rate, and in oxygen consumption was detected in DEX-CGC. Moreover, the activity of the antioxidant enzyme catalase was significantly decreased in DEX-CGC. A similar decrease in catalase activity was observed in cerebellar homogenate from newborn and 40-day-old DEX-rats. In conclusion, these results indicate that prenatal exposure to high levels of glucocorticoids induces long-lasting changes in CGC rendering them more sensitive to oxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that prenatal exposure to excess glucocorticoids may lead to long-term neurological consequences becomes a relevant issue.

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Section: Methodscontrasting

confidence: 58%

mentioning

confidence: 99%

Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death

Ahlbom

Gogvadze

Chen

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…In the research, melatonin treatment provided the protection by increasing the survival of glial cells possibly by directly scavenging reactive oxygen species and by indirectly augmenting their antioxidant capacity. Dare et al (2000) reported that developing cerebellar granule cells were protected by antioxidants J118 and 17, b-estradiol from methylmercury-induced apoptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Imosemi¹

2013

Int. J. Morphol.

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SUMMARY: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reacting oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction, and that the embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. ROS can oxidize molecular targets such as DNA, protein, lipid in a process called oxidative stress resulting in cellular dysfunction and in utero death or teratogenicity. This review, consisting of literature search of journals and chapters in books aims at highlighting the importance of the cerebellum in controlling various motor activities in the body, as well as substances affecting cerebellar development with a view of providing an insight to the role antioxidants play in cerebellar development. It is interesting to note that the developing brain (especially the cerebellum, cerebrum and hippocampus) is highly vulnerable to the deleterious effects of ROS. Studies have shown that exposure to oxidants in the first trimester is associated with an increased risk of major congenital anomalies, as most vital organs in the body develop and some become functional within this period in offspring. Antioxidants may prevent oxidative damage in degenerative diseases including ageing, cardiovascular diseases, cancer, Alzheimer's disease, stroke and Parkinson's disease as such play a critical role in wellness and health maintenance. INTRODUCTIONThe consumption of some drugs and chemical substances at various doses could cause malformations in certain developing body organs especially when used during critical periods of development. Such malformations could reflect in the gross and microscopic appearances of affected organs in the mature organisms (Moore & Persaud, 1998). The critical stages of development at which such malformations occur in mammals correspond to the pre-natal and early postnatal lives. In the former circumstance, these substances when consumed by the mother, affect the embryos or foetus only if they cross the blood placental barrier. In the latter circumstance, the substances need to have been administered directly to the neonates or suckled in the breast milk in early post-natal life for them to affect development (Moore & Persaud).The cerebellum is a highly organized structure in which the Purkinje cells (Pc) are the sole output of the cerebellar cortex (Altman, 1969(Altman, , 1972a(Altman, , 1972b(Altman, , 1972c, and it is one of the first structure of the brain to differentiate, however, it achieves its mature configuration many months after birth (Wang & Zoghbi, 2001;Bouet et al., 2005). For this reason, the cerebellum is especially vulnerable to developmental irregularities on exposure to oxidants which generate free radicals resulting in oxidative stress (Wang & Zoghbi;Kern & Jones, 2006). Oxidative stress occurs due to an imbalance in pro-oxidant and antioxidant levels. Scientific evidence sugg...

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“…It is possibly one of the common mechanisms behind both aluminum and mercury toxicity. Mercury-induced apoptosis has been reported in neural cells (Dare et al 2000;Kunimoto 1994;Miura et al 1999;Takai et al 1998), and there is evidence of a connection between aluminum and the induction of apoptosis (Ghribi et al 2002;Guo and Liang 2001;Savory et al 2001). It has been proposed that glial cells accumulate neurotoxic metals, go to apoptosis, and, consequently, mediate neuronal degeneration (Ohgoh et al 2000;Suarez-Fernandez et al 1999;Young 1992).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and methylmercury in cell lines of neural origin

Toimela

Tähti

2004

Arch Toxicol

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Mercury and aluminum are considered to be neurotoxic metals, and they are often connected with the onset of neurodegenerative diseases. In this study, mercuric mercury, methylmercury and aluminum were studied in three different cell lines of neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis induced by the metals were measured after various incubation times. SH-SY5Y neuroblastoma, U 373MG glioblastoma, and RPE D407 retinal pigment epithelial cells were subcultured to appropriate cell culture plates and 0.01-1,000 microM concentrations of methylmercury, mercuric and aluminum chloride were added into the growth medium. In the assay measuring the mitochondrial dehydrogenase activity, WST-1, the cultures were exposed for 15 min, 24 or 48 h before measurement. Cells were allowed to recover from the exposure in part of the study. Apoptosis induced by the metals was measured after 6-, 24- and 48-h exposure times with the determination of activated caspase 3 enzyme. Mitochondrial assays showed a clear dose-response and exposure time-response to the metals. The most toxic was methylmercury (EC50 ~0.8 microM, 48 h), and the most sensitive cell line was the neuroblastoma cell line SH-SY5Y. Furthermore, there was marked mitochondrial activation, especially in connection with aluminum and methylmercury at low concentrations. This activation may be important during the initiation of cellular processes. All the metals tested induced apoptosis, but with a different time-course and cell-line specificity. In microscopic photographs, glioblastoma cells formed fibrillary tangles, and neuroblastoma cells settled along the fibrilles in cocultures of glial and neuronal cell lines during aluminum exposure. The study emphasized the toxicity of methylmercury to neural cells and showed that aluminum alters various cellular activities.

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Antioxidants J811 and 17?-estradiol protect cerebellar granule cells from methylmercury-induced apoptotic cell death

Cited by 85 publications

References 44 publications

Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death

Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death

The Role of Antioxidants in Cerebellar Development: A Review of Literature

Mitochondrial viability and apoptosis induced by aluminum, mercuric mercury and methylmercury in cell lines of neural origin

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