Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jul;1767(7):980-8.
doi: 10.1016/j.bbabio.2007.04.002. Epub 2007 Apr 14.

Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide

Alessandra Zulian  1 , Valeria Petronilli, Sergio Bova, Federica Dabbeni-Sala, Gabriella Cargnelli, Maurizio Cavalli, David Rennison, Jessica Stäb, Olivia Laita, Dong Jun Lee, Margaret A Brimble, Brian Hopkins, Paolo Bernardi, Fernanda Ricchelli
Affiliations
Free article

Assessing the molecular basis for rat-selective induction of the mitochondrial permeability transition by norbormide

Alessandra Zulian et al. Biochim Biophys Acta. 2007 Jul.
Free article

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.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

Publication types

LinkOut - more resources