17β-estradiol modulates mitochondrial Ca²⁺ flux in rat caudate nucleus and brain stem.
The aim of this study was to examine the rapid non-genomic effect of 17β-estradiol (E2) on Ca(2+) transport in mitochondria isolated from the nerve terminals (synaptosomes) of caudate nuclei (NC) and brain stems (BS) of ovariectomised female rats. In physiological conditions no effect of E2 on Ca(2+) influx into synaptosomal mitochondria through ruthenium red (RR)-sensitive uniporter was observed. However, in the presence of uncoupling agent carbonyl cyanide4-(trifluoromethoxy)phenylhydrazone (FCCP) (1μmol/l), pre-treatment with 0.5nmol/l E2 protected mitochondrial membrane potential and consequently increased Ca(2+) influx (2.3-fold in NC and 3.1-fold in BS). At the same time, 0.5nmol/l E2 by increasing the affinity of mitochondrial Na(+)/Ca(2+) exchanger for Na(+) inhibited mitochondrial Ca(2+) efflux in NC and BS by about 40%. Also, the specific binding of physiological E2 concentrations (0.1-10nmol/l) to isolated synaptosomal mitochondria was detected. Using membrane impermeable E2 bound to bovine serum albumin and selective inhibitor of mitochondrial Na(+)/Ca(2+) exchanger, we obtained that E2's action on mitochondrial Ca(2+) efflux at least partially is due to the direct effects on the mitochondrial membrane and/or Na(+)/Ca(2+) exchanger located in inner mitochondrial membrane. Our results implicate E2 as a modulator of Ca(2+) concentration in mitochondrial matrix, and ultimately in the cytosol. Given the vital role of Ca(2+) in regulation of total nerve cells activity, especially energy metabolism, neurotransmission and directing the cells toward survival or cell death, the effects on mitochondrial Ca(2+) transport could be one of the important modes of E2 neuromodulatory action independent of the genome.
Department of Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinča", University of Belgrade, P.O. Box 522, 11001 Belgrade, Serbia. snjezana5.imr12@yahoo.com
S
S
Petrović
M
M
Milošević
D
D
Drakulić
I
I
Grković
M
M
Stanojlović
N
N
Mitrović
A
A
Horvat
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism
D004958:Estradiol; D002118:Calcium