PMID- 18577698
OWN - NLM
STAT- MEDLINE
DCOM- 20081006
LR  - 20220321
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 295
IP  - 3
DP  - 2008 Sep
TI  - Role of wild-type estrogen receptor-beta in mitochondrial cytoprotection of 
      cultured normal male and female human lens epithelial cells.
PG  - E637-47
LID - 10.1152/ajpendo.90407.2008 [doi]
AB  - 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-beta (ERbeta) 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 ERbeta 
      (wtERbeta1) was also assessed using wtERbeta1 siRNA to suppress expression. A 
      triple-primer PCR assay was employed to determine the proportional distribution 
      of the receptor isoforms (wtERbeta1, -beta2, and -beta5) from the total ERbeta 
      message pool in male and female cell cultures. Irrespective of sex, nHLE express 
      wtERbeta1 and the ERbeta2 and ERbeta5 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 ERbeta2 and ERbeta5 isoforms were 
      distributed primarily in the nucleus and cytosol, respectively; no association 
      with the mitochondria was detected. Both male and female nHLE treated with E(2) 
      (1 muM) displayed similar levels of protection against peroxide-induced oxidative 
      stress. In conjunction with acute oxidative insult, RNA suppression of wtERbeta1 
      elicited the collapse of mitochondrial membrane potential and markedly diminished 
      the otherwise protective effects of E(2). Thus, whereas the estrogen-mediated 
      prevention of mitochondrial membrane permeability transition is sex independent, 
      the mechanism of estrogen-induced mitochondrial cytoprotection is wtERbeta1 
      dependent.
FAU - Flynn, J M
AU  - Flynn JM
AD  - Department of Cell Biology, University of North Texas Health Science Center, Fort 
      Worth, TX, USA.
FAU - Dimitrijevich, S D
AU  - Dimitrijevich SD
FAU - Younes, M
AU  - Younes M
FAU - Skliris, G
AU  - Skliris G
FAU - Murphy, L C
AU  - Murphy LC
FAU - Cammarata, P R
AU  - Cammarata PR
LA  - eng
PT  - Journal Article
DEP - 20080624
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Benzimidazoles)
RN  - 0 (Carbocyanines)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (RNA, Small Interfering)
RN  - 21527-78-6 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine)
SB  - IM
MH  - Benzimidazoles
MH  - Blotting, Western
MH  - Carbocyanines
MH  - Cells, Cultured
MH  - Cytoprotection/*physiology
MH  - Epithelial Cells/*physiology
MH  - Estrogen Receptor beta/drug effects/genetics/*physiology
MH  - Female
MH  - Fluorescent Dyes
MH  - Humans
MH  - Immunohistochemistry
MH  - Lens, Crystalline/*cytology
MH  - Male
MH  - Microscopy, Confocal
MH  - Mitochondria/*physiology
MH  - Mitochondrial Membranes/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Characteristics
EDAT- 2008/06/26 09:00
MHDA- 2008/10/07 09:00
CRDT- 2008/06/26 09:00
PHST- 2008/06/26 09:00 [pubmed]
PHST- 2008/10/07 09:00 [medline]
PHST- 2008/06/26 09:00 [entrez]
AID - 90407.2008 [pii]
AID - 10.1152/ajpendo.90407.2008 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E637-47. doi: 
      10.1152/ajpendo.90407.2008. Epub 2008 Jun 24.