17β-estradiol stimulates MAPK signaling pathway in human lens epithelial cell cultures preventing collapse of mitochondrial membrane potential during acute oxidative stress

17β-estradiol (17β-E2) protects against H2O2-mediated depletion of intracellular ATP and lessens the degree of depolarization of mitochondrial membrane potential (ΔΨm) in cultured lens epithelial cells consequential to oxidative insult. We now report that 17β-E2 acts as a positive regulator of the survival signal transduction pathway, MAPK which, in turn, acts to stabilize ΔΨm, 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 17β-E2 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 17β-E2. Cell cultures were exposed to the MEK1/2 inhibitor, UO126, subsequent to H2O2±17β-E2 treatment and the ΔΨm 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 17β-E2 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 17β-E2 stimulation of ERK1/2 phosphorylation and mitochondrial stabilization that would otherwise cause a complete collapse of ΔΨm.