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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/E637    most recent 90407.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Flynn, J. M. Articles by Cammarata, P. R. Search for Related Content PubMed PubMed Citation Articles by Flynn, J. M. Articles by Cammarata, P. R.

Role of wild-type estrogen receptor-β in mitochondrial cytoprotection of cultured normal male and female human lens epithelial cells

¹Departments of Cell Biology and Genetics and ²Integrative Physiology, University of North Texas Health Science Center, Fort Worth; ³Department of Pathology, Baylor College of Medicine, Houston, Texas; and ⁴Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 30 April 2008 ; accepted in final form 19 June 2008

The influence of sexual category as a modifier of cellular function is underinvestigated. Whether sex differences affect estrogen-mediated mitochondrial cytoprotection was determined using cell cultures of normal human lens epithelia (nHLE) from postmortem male and female donors. Experimental indicators assessed included differences in estrogen receptor-β (ERβ) isoform expression, receptor localization in mitochondria, and estrogen-mediated prevention of loss of mitochondrial membrane potential using the potentiometric fluorescent compound JC-1 after nHLE were exposed to peroxide. The impact of wild-type ERβ (wtERβ1) was also assessed using wtERβ1 siRNA to suppress expression. A triple-primer PCR assay was employed to determine the proportional distribution of the receptor isoforms (wtERβ1, -β2, and -β5) from the total ERβ message pool in male and female cell cultures. Irrespective of sex, nHLE express wtERβ1 and the ERβ2 and ERβ5 splice variants in similar ratios. Confocal microscopy and immunofluorescence revealed localization of the wild-type receptor in peripheral mitochondrial arrays and perinuclear mitochondria as well as nuclear staining in both cell populations. The ERβ2 and ERβ5 isoforms were distributed primarily in the nucleus and cytosol, respectively; no association with the mitochondria was detected. Both male and female nHLE treated with E₂ (1 µM) displayed similar levels of protection against peroxide-induced oxidative stress. In conjunction with acute oxidative insult, RNA suppression of wtERβ1 elicited the collapse of mitochondrial membrane potential and markedly diminished the otherwise protective effects of E₂. Thus, whereas the estrogen-mediated prevention of mitochondrial membrane permeability transition is sex independent, the mechanism of estrogen-induced mitochondrial cytoprotection is wtERβ1 dependent.