title: Dehydroepiandrosterone with other neurosteroids preserve neuronal mitochondria from calcium overload.
abstract: 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.
authors: Department of Pharmacology, University of Tartu, Ravila 19, 50411 Tartu, Estonia. allen@ut.ee
authors: Allen
authors: A
authors: Kaasik
authors: Dzhamilja
authors: D
authors: Safiulina
authors: Anti
authors: A
authors: Kalda
authors: Alexander
authors: A
authors: Zharkovsky
mesh_terms: 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*
chemical_list: D018696:Neuroprotective Agents; D012503:Saponins; D013256:Steroids; D003687:Dehydroepiandrosterone; D002118:Calcium