Biological effects of anionic meso-tetrakis (para-sulfonatophenyl) porphyrins modulated by the metal center. Studies in rat liver mitochondria.
In this paper, we present a study about the influence of the porphyrin metal center and meso ligands on the biological effects of meso-tetrakis porphyrins. Different from the cationic meso-tetrakis 4-N-methyl pyridinium (Mn(III)TMPyP), the anionic Mn(III) meso-tetrakis (para-sulfonatophenyl) porphyrin (Mn(III)TPPS4) exhibited no protector effect against Fe(citrate)-induced lipid oxidation. Mn(III)TPPS4 did not protect mitochondria against endogenous hydrogen peroxide and only delayed the swelling caused by tert-BuOOH and Ca2+. Fe(III)TPPS4 exacerbated the effect of the tert-BuOOH, and both porphyrins did not significantly affect Fe(II)citrate-induced swelling. Consistently, Fe(III)TPPS4 predominantly promotes the homolytic cleavage of peroxides and exhibits catalytic efficiency ten-fold higher than Mn(III)TPPS4. For Mn(III)TPPS4, the microenvironment of rat liver mitochondria favors the heterolytic cleavage of peroxides and increases the catalytic efficiency of the manganese porphyrin due to the availability of axial ligands for the metal center and reducing agents such as glutathione (GSH) and proteins necessary for Compound II (oxomanganese IV) recycling to the initial Mn(III) form. The use of thiol reducing agents for the recycling of Mn(III)TPPS4 leads to GSH depletion and protein oxidation and consequent damages in the organelle.
Pessoto
Felipe Samuel
FS
Departamento de Bioquímica, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
Inada
Natalia Mayumi
NM
Nepomuceno
Maria de Fátima
Mde F
Ruggiero
Ana Célia
AC
Nascimento
Otaciro R
OR
Vercesi
Anibal E
AE
Nantes
Iseli L
IL
D000818:Animals; D000838:Anions; D004578:Electron Spin Resonance Spectroscopy; D005453:Fluorescence; D008670:Metals / Q000737:chemistry*; D008930:Mitochondria, Liver / Q000187:drug effects*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000838:Anions; D008670:Metals; D011166:Porphyrins