Mechanistic aspects of 1-methyl-4-phenyl pyridinium iodide toxicity in Escherichia coli: the role of oxygen and hydrogen peroxide.
1-Methyl-4-phenyl pyridinium iodide (MPP+) and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies in a variety of systems have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the Escherichia coli model and demonstrated that MPP+ is toxic to bacterial cells in dose- and time-dependent modes. Additionally, it is shown that only in the presence of molecular oxygen did bacterial inactivation occur. This requirement for oxygen can be circumvented by adventitious H2O2. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity.
Haskel
Y
Y
Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.
Udassin
R
R
Chevion
M
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism; D000332:Aerobiosis; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D005609:Free Radicals; D006639:Histidine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D020267:MPTP Poisoning; D008353:Mannitol / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D013997:Time Factors
D005609:Free Radicals; D008353:Mannitol; D006639:Histidine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006861:Hydrogen Peroxide; D010100:Oxygen