The effects of β-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and β-amyloid secretion

doi:10.1016/S0306-4522(02)00211-7

Neuroscience

Volume 113, Issue 4, 10 September 2002, Pages 849-855

https://doi.org/10.1016/S0306-4522(02)00211-7 Get rights and content

Abstract

The role of estrogen as a neurotrophic/neuroprotective agent in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases is increasingly being shown. In this study we examine the neuroprotective effects of β-estradiol on SHSY5Y neuroblastoma cells which have been exposed to the heavy metals cobalt and mercury. The results show that cobalt and mercury are able to induce oxidative stress and cell cytotoxicity and increase the secretion of β-amyloid 1–40 and 1–42. These deleterious effects are reversed by the pretreatment of cells with β-estradiol. It is further shown that β-estradiol exerts its neuroprotective action through mechanisms which reduce oxidative stress and reduce β-amyloid secretion. Pre-treatment of the cells with α-estradiol did not alleviate the toxic effects of the heavy metals.

Our results are significant as they contribute to a better understanding of the mode of action of estrogen with relevance to its use in the treatment of neurodegenerative disorders.

Section snippets

Cell culture

SHSY5Y neuroblastoma cells were grown in complete minimum essential medium (MEM) in a humidified air/5% CO₂ chamber at 37°C. Sixteen hours prior to treatment cells were washed free of fetal calf serum (FCS) containing medium and further incubated in FCS-free MEM containing the neuroblastoma growth supplement N2. All cell culture materials were purchased from Gibco Life Technologies (Rockville, MD, USA) unless otherwise stated. The use of H₂O₂, CoCl₂ and HgCl₂ (Sigma, St. Louis, MO, USA) at the

Results

Exposure of SHSY5Y cells for 24 h to β-estradiol, at the physiological concentrations of 0–100 nM, produced no significant alteration of cell viability (Fig. 1A). The exposure of cells to 300 μM CoCl₂ or 180 nM HgCl₂ resulted in significant induction of cell cytotoxicity shown by loss of cell viability (Fig. 1B). H₂O₂ (50 μM), a known stress inducer, was included as a positive control and significantly affected cell viability (Fig. 1B). The preincubation of cells for 24 h with 10 nM β-estradiol

Discussion

Hydrogen peroxide, CoCl₂ and HgCl₂ were all able to induce oxidative stress and cell cytotoxicity and affect Aβ secretion in SHSY5Y cells. β-Estradiol pretreatment of cells resulted in a significant protection against CoCl₂ and HgCl₂ induced oxidative stress and cell cytotoxicity. β-Estradiol was, however, unable to protect cells against H₂O₂ induced oxidative stress and cell cytotoxicity. The explanation for this lies in the concentration of β-estradiol used in this study, 10 nM. It appears

Conclusion

This study has shown that β-estradiol at physiological concentrations is able to protect neuronal cells from cobalt and mercury induced oxidative stress, cell cytotoxicity and Aβ secretion. These findings are significant as they demonstrate that the use of estrogen could reduce the risk of heavy metal induced neurodegeneration.

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The effects of β-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and β-amyloid secretion

Abstract

Section snippets

Cell culture

Results

Discussion

Conclusion

Brain Res. Rev.

Cell

Biochem. Biophys. Res. Commun.

Neurobiol. Aging

Biochem. Biophys. Res. Commun.

J. Steroid Biochem.

Free Radical Biol. Med.

Brain Res.

Neuroscience

J. Biol. Chem.

Steroids

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Brain Res.

J. Biol. Chem.

Toxicol. Lett.

Lancet

Neurotoxicology

Am. J. Clin. Nutr.

J. Biol. Chem.

Toxicol. Lett.

Regulation of antioxidant enzyme activities in the male and female rat macrophages by sex steroids

Braz. J. Med. Biol. Res.

Neuroprotection against oxidative stress by estrogens: structure-activity relationship

Mol. Pharmacol.

17-Beta-estradiol enhances the outgrowth and survival of neocortical neurons in culture

Neurochem. Res.

Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain

Neurotoxicology

Sodium salicylate and 17β-estradiol attenuate nuclear transcription factor NF-κB translocation in cultured rat astroglial cultures following exposure to amyloid Aβ1–40 and lipopolxsaccharides

J. Neurochem.

Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors

J. Neurosci.

Brain trace elements in Alzheimer’s disease

Neurotoxicology

The steroid and thyroid hormone receptor superfamily

Science