Modulation of Bcl‐2 expression: a potential component of estrogen protection in NT2 neurons

EUROPROTECTIVE effects of estrogen have been demonstrated against a variety of cytotoxic insults. We present data here addressing a possible mechanism of estrogen neuroprotection in the human teratocarcinoma cell line NT2 terminally differentiated to a neuronal phenotype. Cell death induced by H2O2 or glutamate results in a dose-dependent cell death of NT2 neurons, while 24 h of estrogen pretreatment significantly enhances neuronal viability. Bcl-2 expression has been shown to reduce oxidative stress and prevent cell death. In NT2 neurons, Bcl-2 levels are dramatically elevated upon differentiation and are further enhanced with estrogen treatment. These results suggest that neuroprotective effects of estrogen may be related to increases in Bcl-2 expression.

[1]  P. Mcgonigle,et al.  Excitotoxic cell death and delayed rescue in human neurons derived from NT2 cells , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  J. Simpkins,et al.  Estradiol Treatment Increases Viability of Glioma and Neuroblastoma Cells in Vitro , 1994, Molecular and Cellular Neuroscience.

[3]  V M Lee,et al.  Pure, postmitotic, polarized human neurons derived from NTera 2 cells provide a system for expressing exogenous proteins in terminally differentiated neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  V. Henderson,et al.  Estrogen deficiency and risk of Alzheimer's disease in women. , 1994, American journal of epidemiology.

[5]  M. Nakano,et al.  Estrogens as natural antioxidants of membrane phospholipid peroxidation , 1987, FEBS letters.

[6]  J. Simpkins,et al.  Low concentrations of estradiol reduce β-amyloid (25–35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells , 1997, Brain Research.

[7]  A. Mooradian Antioxidant properties of steroids , 1993, The Journal of Steroid Biochemistry and Molecular Biology.

[8]  J. Simpkins,et al.  Estradiol protects against β-amyloid (25–35)-induced toxicity in SK-N-SH human neuroblastoma cells , 1996, Neuroscience Letters.

[9]  A. Davies The Bcl-2 family of proteins, and the regulation of neuronal survival , 1995, Trends in Neurosciences.

[10]  J. Simpkins,et al.  17α-Estradiol Exerts Neuroprotective Effects on SK-N-SH Cells , 1997, The Journal of Neuroscience.

[11]  A. Kriegstein,et al.  Glutamate neurotoxicity in cortical cell culture , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  E. Hall,et al.  Sex Differences in Postischemic Neuronal Necrosis in Gerbils , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.