Inhibition of mitochondrial permeability transition by polyamines and magnesium: importance of the number and distribution of electric charges.
The protective effects of Mg2+ and various natural and synthetic polyamines on the permeability transition of isolated rat liver mitochondria have been compared. The permeability transition was induced by incubating the mitochondria in a sucrose medium at pH 7.4 in the presence of 100 microM Ca2+ and 1 mM phosphate and was monitored via the release of endogenous Mg2+, sucrose permeation, mitochondria swelling and the fall of transmembrane potential. By all of these parameters (only the traces of delta psi have been reported) spermine fully inhibited the transition at 25 microM concentration, spermidine and caldine at 250 microM and Mg2+ at 500 microM concentration. Both putrescine and dien exhibited only a partial protection even at 2.5 mM concentration. The protective action resulted strictly dependent on the number of the positive charges of each cation. In the case of polyamines this number is also determined by the nature of the methylene carbon chains of each compound.
Tassani
V
V
Dipartimento di Chimica Biologica, Università di Padova, Italy.
Biban
C
C
Toninello
A
A
Siliprandi
D
D
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D010539:Permeability; D010710:Phosphates / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D010710:Phosphates; D011073:Polyamines; D013096:Spermine; D008274:Magnesium; D002118:Calcium; D013095:Spermidine; D011700:Putrescine