Manganese corroles prevent intracellular nitration and subsequent death of insulin-producing cells.
Reactive oxygen species are heavily involved in the pathogenesis of diabetes mellitus (DM) because the insulin-producing beta cells are particularly vulnerable to free-radical-mediated cytotoxicity. Catalytic anti-oxidants have been successfully applied for attenuation of DM and its consequences, but most recent research revealed that preventing the nitration of vital proteins/enzymes might be an even more powerful strategy. We now report an unprecedented efficiency of manganese(III) corroles regarding the protection of rat pancreatic beta cells against intracellular nitration by peroxynitrite and subsequent cell death. A comparison between analogous corroles and porphyrin metal complexes reveals significant superiority of the former in all examined aspects. This is particularly true for the positively-charged manganese(III) corrole, which decomposes peroxynitrite fast enough and through a unique catalytic mechanism that is devoid of potentially nitrating reaction intermediates.
Okun
Zoya
Z
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Kupershmidt
Lana
L
Amit
Tamar
T
Mandel
Silvia
S
Bar-Am
Orit
O
Youdim
Moussa B H
MB
Gross
Zeev
Z
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D007328:Insulin / Q000096:biosynthesis*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008345:Manganese / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism*; D051381:Rats
D007328:Insulin; D009566:Nitrates; D008345:Manganese