title: Estradiol protects against ATP depletion, mitochondrial membrane potential decline and the generation of reactive oxygen species induced by 3-nitroproprionic acid in SK-N-SH human neuroblastoma cells.
abstract: Mitochondria are recognized as modulators of neuronal viability during ischemia, hypoxia and toxic chemical exposure, wherein mitochondria dysfunction leading to ATP depletion may be a common pathway of cell death. Estrogens have been reported to be neuroprotective and proposed to play a role in the modulation of cerebral energy/glucose metabolism. To address the involvement of 17beta-estradiol preservation of mitochondrial function, we examined various markers of mitochondrial activity in human SK-N-SH neuroblastoma cells exposed to 3-nitroproprionic acid (3-NPA), a succinate dehydrogenase inhibitor which uncouples oxidative phosphorylation. 3-NPA (10 mM) significantly increased ATP levels at 2 h then caused a 40% and a 50% decrease in ATP levels from baseline when treated for 12 h and 24 h, respectively. 3-NPA also induced significant increases in levels of cellular hydrogen peroxide and peroxynitrite at 2 h and a 60% decrease in mitochondrial membrane potential (MMP) at 12 h exposure. 17beta-Estradiol (17beta-E(2)) pretreatment restored the ATP level back to 80% at 12 h of that in control cells treated with 3-NPA but without E(2), blunted the effect of 3-NPA on MMP and reactive oxygen species levels. The present study indicates that 17beta-E(2) can preserve mitochondrial function in the face of inhibition of oxidative phosphorylation.
authors.affiliation: Department of Pharmacodynamics and Center for Neurobiology of Aging, University of Florida, Gainesville, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: P S
authors.initials: PS
authors.lastname: Green
authors.forename: J W
authors.initials: JW
authors.lastname: Simpkins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000648:ultrastructure*; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure*; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014475:Uncoupling Agents
chemical_list: D004791:Enzyme Inhibitors; D009574:Nitro Compounds; D011422:Propionates; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D004958:Estradiol; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid