Biapigenin modulates the activity of the adenine nucleotide translocator in isolated rat brain mitochondria.
In this study, we investigated the effects of biapigenin, a biflavone present in the extracts of Hypericum perforatum, in rat brain mitochondrial bioenergetics and calcium homeostasis. We found that biapigenin significantly decreased adenosine diphosphate (ADP)-induced membrane depolarization and increased repolarization (by 68 and 37%, respectively). These effects were blocked by atractyloside and bongkrekic acid, but not oligomycin. In the presence of biapigenin, an ADP-stimulated state 3 respiration was still noticeable, which did not happen in the presence of adenine nucleotide translocator (ANT) inhibitors. Taking in consideration the relevance of the ANT in the modulation of the mitochondrial permeability transition pore (mPTP), mitochondrial calcium homeostasis was evaluated alone or in the presence of biapigenin. We found that biapigenin reduces mitochondrial calcium retention by increasing calcium efflux, an effect that was blocked by ADP plus oligomycin, an efficient blocker of the mPTP in brain mitochondria. Taken together, the results in this article suggest that biapigenin modulates mPTP opening, possibly by modulating ANT function, contributing for enhanced mitochondrial calcium efflux, thereby reducing calcium burden and contributing for neuroprotection against excitotoxicity.
Silva
Bruno A
BA
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Oliveira
Paulo J
PJ
Cristóvão
Armando
A
Dias
Alberto C P
AC
Malva
João O
JO
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D001921:Brain / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D044946:Biflavonoids; D004791:Enzyme Inhibitors; D009840:Oligomycins; C446502:biapigenin; D047310:Apigenin; D000226:Mitochondrial ADP, ATP Translocases; D000251:Adenosine Triphosphatases; D002118:Calcium