MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gridley, K. E.
Right arrow Articles by Simpkins, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gridley, K. E.
Right arrow Articles by Simpkins, J. W.

Vol. 54, Issue 5, 874-880, November 1998

A Novel, Synergistic Interaction Between 17 beta -Estradiol and Glutathione in the Protection of Neurons against beta -Amyloid 25-35-Induced Toxicity In Vitro

Kelly E. Gridley, Pattie S. Green, and James W. Simpkins

Department of Pharmacodynamics and Center for Neurobiology of Aging, College of Pharmacy, University of Florida, Gainesville, Florida 32610

The present studies were undertaken to investigate the possibility of an interaction between 17 beta -estradiol (E2) and glutathione in protecting cells against the presence of beta -amyloid 25-35 (beta AP 25-35). We demonstrate that when evaluated individually, supraphysiological concentrations of either E2 (200 nM) or of reduced glutathione (GSH; 325 µM) can protect SK-N-SH human neuroblastoma cells from beta AP 25-35 (20 µM) toxicity. This dose of beta AP 25-35 was chosen based on the LD50 (28.9 µM) obtained in our earlier work. However, in the presence of 3.25 µM GSH, the neuroprotective EC50 of E2 was shifted from 126 ± 89 nM to 0.033 ± 0.031 nM, approximately 4000-fold. Similarly, in primary rat cortical neurons, the addition of GSH (3.25 µM) increased the potency of E2 against beta AP 25-35 (10 µM) toxicity, as evidenced by a shift in the EC50 values of E2 from 68 ± 79 nM in the absence of GSH to 4 ± 6 nM in its presence. The synergy between E2 and GSH was not antagonized by the addition of the estrogen receptor antagonist, ICI 182,780. Other thiol-containing compounds did not interact synergistically with E2, nor were any synergistic interactions observed between E2 and ascorbic acid or alpha -tocopherol. Based on these data, we propose an estrogen-receptor independent synergistic interaction between glutathione and E2 that dramatically increases the neuroprotective potency of the steroid and may provide insight for the development of new treatment strategies for neurodegenerative diseases.

Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Therapeutic Advances in Neurological DisordersHome page
J. W. Simpkins, E. Perez, Xiaofei Wang, ShaoHua Yang, Yi Wen, and M. Singh
Review: The potential for estrogens in preventing Alzheimer's disease and vascular dementia
Therapeutic Advances in Neurological Disorders, January 1, 2009; 2(1): 31 - 49.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. M. Flynn, S. D. Dimitrijevich, M. Younes, G. Skliris, L. C. Murphy, and P. R. Cammarata
Role of wild-type estrogen receptor-{beta} in mitochondrial cytoprotection of cultured normal male and female human lens epithelial cells
Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E637 - E647.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. W. Irwin, J. Yao, R. T. Hamilton, E. Cadenas, R. D. Brinton, and J. Nilsen
Progesterone and Estrogen Regulate Oxidative Metabolism in Brain Mitochondria
Endocrinology, June 1, 2008; 149(6): 3167 - 3175.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. D. Yi, Z. Y. Cai, D. F. Covey, and J. W. Simpkins
Estrogen Receptor-Independent Neuroprotection via Protein Phosphatase Preservation and Attenuation of Persistent Extracellular Signal-Regulated Kinase 1/2 Activation
J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1188 - 1195.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
X. Wang, J. A. Dykens, E. Perez, R. Liu, S. Yang, D. F. Covey, and J. W. Simpkins
Neuroprotective Effects of 17beta-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells
Mol. Pharmacol., July 1, 2006; 70(1): 395 - 404.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. Kurata, M. Takebayashi, S. Morinobu, and S. Yamawaki
{beta}-Estradiol, Dehydroepiandrosterone, and Dehydroepiandrosterone Sulfate Protect against N-Methyl-D-aspartate-Induced Neurotoxicity in Rat Hippocampal Neurons by Different Mechanisms
J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 237 - 245.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
X. Wang, J. W. Simpkins, J. A. Dykens, and P. R. Cammarata
Oxidative Damage to Human Lens Epithelial Cells in Culture: Estrogen Protection of Mitochondrial Potential, ATP, and Cell Viability
Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2067 - 2075.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. W. Singleton, Y. Feng, C. J. Burd, and S. A. Khan
Nongenomic Activity and Subsequent c-fos Induction by Estrogen Receptor Ligands Are Not Sufficient to Promote Deoxyribonucleic Acid Synthesis in Human Endometrial Adenocarcinoma Cells
Endocrinology, January 1, 2003; 144(1): 121 - 128.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
Y.-H. Suh and F. Checler
Amyloid Precursor Protein, Presenilins, and alpha -Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer's Disease
Pharmacol. Rev., September 1, 2002; 54(3): 469 - 525.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
L. D. McCullough, N. J. Alkayed, R. J. Traystman, M. J. Williams, and P. D. Hurn
Postischemic Estrogen Reduces Hypoperfusion and Secondary Ischemia After Experimental Stroke
Stroke, March 1, 2001; 32(3): 796 - 802.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
T. K. Toung, P. D. Hurn, R. J. Traystman, F. E. Sieber, and F. M. Faraci
Estrogen Decreases Infarct Size After Temporary Focal Ischemia in a Genetic Model of Type 1 Diabetes Mellitus Editorial Comment
Stroke, November 1, 2000; 31(11): 2701 - 2706.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
H. SAWADA, M. IBI, T. KIHARA, M. URUSHITANI, K. HONDA, M. NAKANISHI, A. AKAIKE, and S. SHIMOHAMA
Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons
FASEB J, June 1, 2000; 14(9): 1202 - 1214.
[Abstract] [Full Text]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
H. Sawada, F. Udaka, Y. Izumi, K. Nishinaka, H. Kawakami, S. Nakamura, and M. Kameyama
Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease
J. Neurol. Neurosurg. Psychiatry, May 1, 2000; 68(5): 653 - 656.
[Abstract] [Full Text]

Home page
 StrokeHome page
K. Sampei, S. Goto, N. J. Alkayed, B. J. Crain, K. S. Korach, R. J. Traystman, G. E. Demas, R. J. Nelson, P. D. Hurn, and S. Piper Duckles
Stroke in Estrogen Receptor-{alpha}-Deficient Mice • Editorial Comment
Stroke, March 1, 2000; 31(3): 738 - 744.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. J. Manly, C. A. Merchant, D. M. Jacobs, S. A. Small, K. Bell, M. Ferin, and R. Mayeux
Endogenous estrogen levels and Alzheimer's disease among postmenopausal women
Neurology, February 22, 2000; 54(4): 833 - 837.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1998 by the American Society for Pharmacology and Experimental Therapeutics