Protective effect of N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine (PF9601N) on mitochondrial permeability transition.
PF9601N, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine, an monoamine oxidase (MAO) B inhibitor, has shown neuroprotective properties against dopaminergic toxins. To elucidate the mechanisms involved in this protection, the effect of PF9601N on mitochondria was assessed. PF9601N prevents mitochondrial swelling, drop in the electrical potential and oxidation of sulfhydryl groups, glutathione and pyridine nucleotides induced by Ca(2+). These observations demonstrate the protective effect of PF9601N on the induction of mitochondrial permeability transition. This protection is due to the interaction of the secondary protonated amino group in the molecule with pore-forming structures and to its antioxidant property, rather than to inhibition of MAO B activity. PF9601N also prevents the release of cytochrome c from mitochondria, suggesting its potential inhibitory effect on mitochondria-mediated apoptosis. The low IC(50) value for this inhibition, in comparison with deprenyl, make it a more efficient compound than propargylamines and other amines in protecting the bioenergetic functions of mitochondria.
Battaglia
V
V
Dipartimento di Chimica Biologica, Università di Padova, and Istituto di Neuroscienze del C.N.R., Unità per lo studio delle Biomembrane, Viale G. Colombo 3, 35121 Padova, Italy.
Sanz
E
E
Salvi
M
M
Unzeta
M
M
Toninello
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
D007211:Indoles; C470996:N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine; D013438:Sulfhydryl Compounds; D045304:Cytochromes c; D010100:Oxygen; D002118:Calcium