Journal
MITOCHONDRION
Volume 5, Issue 4, Pages 235-247Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2005.01.004
Keywords
ERK; estrogen; hydrogen peroxide; human lens epithelial cell; mitochondria
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Funding
- NEI NIH HHS [EY02027, EY05570, R24 EY014803, R01 EY005570, R01 EY002027] Funding Source: Medline
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17 beta-estradiol (17 beta-E-2) protects against H2O2-mediated depletion of intracellular ATP and lessens the degree of depolarization of mitochondrial membrane potential (Delta Psi(m)) in cultured lens epithelial cells consequential to oxidative insult. We now report that 17 beta-E-2 acts as a positive regulator of the survival signal transduction pathway, MAPK which, in turn, acts to stabilize Delta Psi(m), in effect, attenuating the extent of depolarization of mitochondrial membrane potential in the face of acute oxidative stress. The SV-40 viral transformed human cell line, HLE-B3 was treated with 17 beta-E-2 over a time course of 60 min and phosphorylation of ERK1/2 was analyzed by Western blot. ERK1/2 was phosphorylated within 5-15 min in the presence of 17 beta-E-2. Cell cultures were exposed to the MEK1/2 inhibitor, UO126, subsequent to H2O2 +/- 17 beta-E-2 treatment and the Wpm examined using JC-1, a potentiometric dye which serves as an indicator for the state of mitochondrial membrane potential. UO126 treatment attenuated ERK1/2 phosphorylation irrespective of whether estradiol was administered. Mitochondrial membrane depolarization resulting from H2O2 Stress was substantially greater in the presence of UO126. The greater the extent of depolarization, the less effective 17 beta-E-2 treatment was in checking mitochondrial membrane depolarization, indicating that the relative degree of ERK phosphorylation influences mitochondrial stability with oxidative insult. The data support a positive correlation between 17 beta-E-2 stimulation of ERK1/2 phosphorylation and mitochondrial stabilization that would otherwise cause a complete collapse of Delta Psi(m). (c) 2005 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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