Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide (Articolo in rivista)

Type
Label
  • Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bbabio.2007.04.002 (literal)
Alternative label
  • Zulian A; Petronilli V; Bova S; Dabbeni-Sala F; Cargnelli G; Cavalli M; Rennison D; Stäb J; Laita O; Lee DJ; Brimble MA; Hopkins B; Bernardi P; Ricchelli F (2007)
    Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide
    in Biochimica et biophysica acta. Bioenergetics
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Zulian A; Petronilli V; Bova S; Dabbeni-Sala F; Cargnelli G; Cavalli M; Rennison D; Stäb J; Laita O; Lee DJ; Brimble MA; Hopkins B; Bernardi P; Ricchelli F (literal)
Pagina inizio
  • 980 (literal)
Pagina fine
  • 988 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 1767 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 7 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Rennison D, Brimble MA, Stab J, Laita O, Lee DJ, University of Auckland, Auckland, New Zealand; Bova S, Cavalli M, Zulian A, Dabbeni-Sala F, Cargnelli G, Bernardi P, University of Padova; Hopkins B, Landcare Research, Lincoln, New Zealand; Ricchelli F, Petronilli V, CNR (literal)
Titolo
  • Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide (literal)
Abstract
  • It was recently demonstrated that the rat-selective toxicant norbormide also induces rat-selective opening of the permeability transition pore (PTP) in isolated mitochondria. Norbormide is a mixture of endo and exo stereoisomers; however, only the endo forms are lethal to rats. In the present study we tested both endo and exo isomers as well as neutral and cationic derivatives of norbormide to: (i) verify if the PTP-regulatory activity by norbormide is stereospecific; (ii) define the structural features of norbormide responsible for PTP-activation, (iii) elucidate the basis for the drug species-specificity. Our results show that: (i) norbormide isomers affect PTP in a rat-selective fashion; however, no relevant differences between lethal and non-lethal forms are observed suggesting that drug regulation of PTP-activity and lethality in rats are unrelated phenomena; (ii) a (phenylvinyl)pyridine moiety represents the key element conferring the PTP-activating effect; (iii) cationic derivatives of rat-active compounds accumulate in the matrix via the membrane potential and activate the PTP also in mouse and guinea pig mitochondria. These findings suggest that the norbormide-sensitive PTP-target is present in all species examined, and is presumably located on the matrix side. The species-selectivity may depend on the unique properties of a transport system allowing drug internalisation in rat mitochondria. (literal)
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