197 - Reversal of BRAF Resistance via Re-Establishment of Redox Balance Using a Unique Anti-Oxidant Strategy

Frank L Meyskens,Feng Liu-Smith,Tcharles Fagundes

doi:10.1016/j.freeradbiomed.2014.10.303

Abstract

197 - Reversal of BRAF Resistance via Re-Establishment of Redox Balance Using a Unique Anti-Oxidant Strategy

Highlights

Powered by the California Digital Library University of California electrode at 25 oC and the dismutation activities, expressed as kcat(H2O2) values, were compared to those of catalase itself, whose kcat(H2O2) value is 1.5 × 106 M-1s-1
We proposed that isoketals induce feed-forward O2– production leading to a vicious cycle of oxidative stress, which contributes to mitochondrial dysfunction and end organ damage
We studied a potential reaction of isoketals with isolated mouse kidney mitochondria, mitochondrial superoxide dismutase (SOD2), and mitochondrial complex I

Summary

Introduction

Powered by the California Digital Library University of California electrode at 25 oC and the dismutation activities, expressed as kcat(H2O2) values, were compared to those of catalase itself, whose kcat(H2O2) value is 1.5 × 106 M-1s-1. The kcat(H2O2) values for 13 cationic Mn(III) N-substituted pyridylporphyrins (MnPs) of high SOD-like activity ranged from 23 to 88 M-1s-1. Analogous Fe(III) N-alkylpyridylporphyrins (FePs) showed ~10-fold higher activity than the corresponding MnPs, but the values were still 4 orders of magnitude lower than that of the enzyme; of note, the kcat(H2O2) values for Fe ethyl and n-octyl analogs were 830 and 360 M-1s-1, respectively.

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Results

Conclusion