TY - JOUR
T1 - Only one of a wide assortment of manganese-containing SOD mimicking compounds rescues the slow aerobic growth phenotypes of both Escherichia coli and Saccharomyces cerevisiae strains lacking superoxide dismutase enzymes
AU - Munroe, William
AU - Kingsley, Carolyn
AU - Durazo, Armando
AU - Butler Gralla, Edith
AU - Imlay, James A.
AU - Srinivasan, Chandra
AU - Selverstone Valentine, Joan
N1 - Funding Information:
This work was supported by grant NIH DK 46828 to J.S.V.
PY - 2007/11
Y1 - 2007/11
N2 - A variety of manganese-containing coordination compounds, frequently termed superoxide dismutase (SOD) mimics, have been reported to have SOD activity in vitro and to be effective at improving conditions related to increased oxidative stress in multicellular organisms. We tested the effectiveness of several of these compounds in substituting for authentic SOD enzymes in two simple systems - the prokaryote Escherichia coli and the single-celled eukaryote, Saccharomyces cerevisiae - where strains are available that completely lack cytoplasmic SOD activity and are thus significantly impaired in their ability to grow aerobically. Most of the compounds tested, including Euk-8 and Euk-134, manganese salen derivatives developed by Eukarion; M40403, a manganese complex of a bis(cyclohexylpyridine)-substituted macrocyclic ligand developed by Metaphore; and several manganese porphyrin derivatives, were ineffective in both systems. Only the manganese tetrapyridyl porphyrin complex MnTM-2-PyP and two close relatives were effective in rescuing aerobic growth of E. coli lacking SOD, and, in the case of sod1Δ yeast, only MnTM-2-PyP itself was fully effective. Surprisingly, several compounds reported to be beneficial in other in vivo model systems (Euk-8, Euk-134, M40403) were actually toxic to these organisms lacking SOD, although they had no effect on the wild-type parent strains. Our results suggest the possibility that the beneficial effects of some of the so-called "SOD mimic drugs" may be due to some property other than in vivo superoxide dismutase activity.
AB - A variety of manganese-containing coordination compounds, frequently termed superoxide dismutase (SOD) mimics, have been reported to have SOD activity in vitro and to be effective at improving conditions related to increased oxidative stress in multicellular organisms. We tested the effectiveness of several of these compounds in substituting for authentic SOD enzymes in two simple systems - the prokaryote Escherichia coli and the single-celled eukaryote, Saccharomyces cerevisiae - where strains are available that completely lack cytoplasmic SOD activity and are thus significantly impaired in their ability to grow aerobically. Most of the compounds tested, including Euk-8 and Euk-134, manganese salen derivatives developed by Eukarion; M40403, a manganese complex of a bis(cyclohexylpyridine)-substituted macrocyclic ligand developed by Metaphore; and several manganese porphyrin derivatives, were ineffective in both systems. Only the manganese tetrapyridyl porphyrin complex MnTM-2-PyP and two close relatives were effective in rescuing aerobic growth of E. coli lacking SOD, and, in the case of sod1Δ yeast, only MnTM-2-PyP itself was fully effective. Surprisingly, several compounds reported to be beneficial in other in vivo model systems (Euk-8, Euk-134, M40403) were actually toxic to these organisms lacking SOD, although they had no effect on the wild-type parent strains. Our results suggest the possibility that the beneficial effects of some of the so-called "SOD mimic drugs" may be due to some property other than in vivo superoxide dismutase activity.
KW - Eukarion
KW - Manganese
KW - Metaphore
KW - Porphyrin
KW - SOD mimic
KW - Superoxide dismutase
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U2 - 10.1016/j.jinorgbio.2007.07.008
DO - 10.1016/j.jinorgbio.2007.07.008
M3 - Article
C2 - 17723242
AN - SCOPUS:35348836631
SN - 0162-0134
VL - 101
SP - 1875
EP - 1882
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 11-12
ER -