Dehydroepiandrosterone with other neurosteroids preserve neuronal mitochondria from calcium overload.
This current study was designed to test whether the dehydroepiandrosterone (DHEA) and other neurosteroids could improve mitochondrial resistance to ischemic damage and cytoplasmic Ca(2+) overload. To imitate these mechanisms at mitochondrial level we treated the saponin permeabilized neurons either with the respiratory chain inhibitor, 1-methyl-4-phenylpyridinium or raised free extra-mitochondrial [Ca(2+)]. Loss of mitochondrial membrane potential (as an indicator of loss of function) was detected by JC-1. The results demonstrate that DHEA partly prevented Ca(2+) overload induced loss of mitochondrial membrane potential but not the loss of potential induced by the inhibitor of the respiratory chain. A similar effect was observed in the presence of other neurosteroids, pregnenolone, pregnanolone and allopregnanolone. DHEA inhibited also the Ca(2+) accumulation to the mitochondria in the presence of Ca(2+) efflux inhibitors. Thus, in the present work we provide evidence that DHEA with several other neurosteroids protect the mitochondria against intracellular Ca(2+) overload by inhibiting Ca(2+) influx into the mitochondrial matrix.
Kaasik
Allen
A
Department of Pharmacology, University of Tartu, Ravila 19, 50411 Tartu, Estonia. allen@ut.ee
Safiulina
Dzhamilja
D
Kalda
Anti
A
Zharkovsky
Alexander
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*
D018696:Neuroprotective Agents; D012503:Saponins; D013256:Steroids; D003687:Dehydroepiandrosterone; D002118:Calcium