title: Chenodeoxycholate is a potent inducer of the permeability transition pore in rat liver mitochondria.
abstract: Several reports support the concept that bile acids may be cytotoxic during cholestatic disease process by causing mitochondrial dysfunction. Here we report additional data and findings aimed at a better understanding of the involvement of the permeability transition pore (PTP) opening in bile acids toxicity. The mitochondrial PTP is implicated as a mediator of cell injury and death in many situations. In the presence of calcium and phosphate, chenodeoxycholic acid (CDCA) induced a permeability transition in freshly isolated rat liver mitochondria, characterized by membrane depolarization, release of matrix calcium, and osmotic swelling. All these events were blocked by cyclosporine A (CyA) and the calcium uniporter inhibitor ruthenium red (RR). The results suggest that CDCA increases the sensitivity of isolated mitochondria in vitro to the calcium-dependent induction of the PTP.
authors.affiliation: Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, Portugal.
authors.forename: A P
authors.initials: AP
authors.lastname: Rolo
authors.forename: P J
authors.initials: PJ
authors.lastname: Oliveira
authors.forename: A J
authors.initials: AJ
authors.lastname: Moreno
authors.forename: C M
authors.initials: CM
authors.lastname: Palmeira
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000633:toxicity*; D002779:Cholestasis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000633:toxicity*; D007202:Indicators and Reagents / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009995:Osmosis / Q000187:drug effects / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology; D013347:Subcellular Fractions
chemical_list: D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; D002635:Chenodeoxycholic Acid; D012430:Ruthenium Red; D016572:Cyclosporine; D002118:Calcium