dc.contributor.author |
Zulian, A |
en |
dc.contributor.author |
Petronilli, V |
en |
dc.contributor.author |
Bova, S |
en |
dc.contributor.author |
Dabbeni-Sala, F |
en |
dc.contributor.author |
Cargnelli, G |
en |
dc.contributor.author |
Cavalli, M |
en |
dc.contributor.author |
Rennison, David |
en |
dc.contributor.author |
Stäb, J |
en |
dc.contributor.author |
Laita, Olivia |
en |
dc.contributor.author |
Lee, Danny |
en |
dc.contributor.author |
Brimble, Margaret |
en |
dc.contributor.author |
Hopkins, Brian |
en |
dc.contributor.author |
Bernardi, P |
en |
dc.contributor.author |
Ricchelli, F |
en |
dc.date.accessioned |
2011-09-19T01:40:46Z |
en |
dc.date.issued |
2007 |
en |
dc.identifier.citation |
Biochim Biophys Acta 1767(7):980-988 Jul 2007 |
en |
dc.identifier.issn |
0005-2728 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/8062 |
en |
dc.description.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. |
en |
dc.language |
EN |
en |
dc.publisher |
Elsevier B.V. |
en |
dc.relation.ispartofseries |
Biochimica et Biophysica Acta-Bioenergetics |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0005-2728/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
norbormide |
en |
dc.subject |
rat-toxicant |
en |
dc.subject |
mitochondria |
en |
dc.subject |
permeability transition |
en |
dc.subject |
species-specificity |
en |
dc.subject |
TOXICANT NORBORMIDE |
en |
dc.subject |
VASOCONSTRICTOR |
en |
dc.subject |
BLOCKING |
en |
dc.title |
Assessing the Molecular Basis for Rat-Selective Induction of the Mitochondrial Permeability Transition by Norbormide |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bbabio.2007.04.002 |
en |
pubs.issue |
7 |
en |
pubs.begin-page |
980 |
en |
pubs.volume |
1767 |
en |
dc.rights.holder |
Copyright: 2007 Elsevier B.V. |
en |
dc.identifier.pmid |
17509521 |
en |
pubs.end-page |
988 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
74188 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Chemistry |
en |
pubs.org-id |
Science Research |
en |
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
17509521 |
en |