The Anticancer Agent Elesclomol Has Direct Effects on Mitochondrial Bioenergetic Function in Isolated Mammalian Mitochondria

Elesclomol ((N-malonyl-bis(N'-methyl-N'-thiobenzoylhydrazide)); formerly STA-4783) is a mitochondria-targeted chemotherapeutic agent that has demonstrated efficacy in selective cancer cell killing in pre-clinical and clinical testing. The biologically active form of elesclomol is a deprotonated copper chelate (elesclomol:copper; E:C), which has been shown to enhance reactive oxygen species (ROS) production and induce a transcriptional gene profile characteristic of an oxidative stress response in vitro. Previous studies suggest that E:C interacts with the electron transport chain (ETC) to generate high levels of ROS within the organelle and ultimately induce cell death. The purpose of this study was to further explore the mechanism of cellular and mitochondrial toxicity of E:C by examining its direct effect on mitochondrial bioenergetic function. The results obtained indicate that E:C treatment in whole cells of non-tumorigenic origin at high concentrations (40 M and higher) induces a rapid and substantial increase in mitochondrial superoxide levels and dissipation of mitochondrial membrane potential. Furthermore, similar higher concentrations of E:C act as a direct uncoupler of oxidative phosphorylation and generalized inhibitor of electron transport activity in isolated, intact mitochondria, and induce a dose-dependent inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity in freeze-thawed mitochondrial preparations. The results of this study are important in that they are the first to demonstrate a direct effect of the E:C chelate on bioenergetic function in isolated mammalian mitochondria, and suggest the possibility that the increase in ROS production and cytotoxicity induced by E:C may in part be due to uncoupling of mitochondrial oxidative phosphorylation and/or inhibition of electron transport activity. These results also provide important information about the mechanisms of mitochondrial and cellular toxicity induced by E:C and will ultimately contribute to a better understanding of the therapeutic potential of elesclomol as an anticancer compound.

The Effect of KHCO3 on Photosynthesis of Eggplant Seedlings

The low concentration of CO2 in the atmosphere is one of the main factors to restrict photosynthesis of C3 plants. The effect of KHCO3 on photosynthesis of eggplant seedlings was studied in order to improve photosynthesis of C3 plants. The results showed that KHCO3 could significantly enhance the photosynthetic rate of eggplant seedlings. 500mg/L KHCO3 was the most optimal concentration to improve photosynthetic rate of eggplant seedlings. KHCO3 could increase light saturation point, CO2 saturation point, carboxylase efficiency and lower CO2 compensate point of eggplant seedlings. KHCO3 could improve stomatal conductance and electron transport activity. There was phosphoenolpyruvate carboxylase (PEPC) in leaves of eggplant seedlings, but PEPC activity was low. KHCO3 could improve ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity and PEPC activity. From impact factors, HCO3- could enhance photosynthetic rate. K+ could raise stomatal conductance of eggplant seedlings. HCO3- could improve activity of PEPC . Both HCO3- and K+ could increase Rubisco activity.

Exposure of Campylobacter jejuni to 6°C: Effects on Heat Resistance and Electron Transport Activity

Human infection with Campylobacter jejuni is frequently associated with the consumption of foods, especially chicken meat, which have been exposed to a range of temperatures during processing, storage, and cooking. Despite the public health importance of C. jejuni, little is known about the effects of cold exposure (refrigeration) on the subsequent ability of this pathogen to survive heat challenge. This work examined the effect of rapid exposure to 6°C for 24 h on the heat resistance at 52°Cof19 C. jejuni strains originally isolated from various sources. The resulting death curves were analyzed with the Weibull model. Unlike cold-exposed cells of Escherichia coli and Salmonella, which have been reported to show significant increased sensitivity to heat, such exposure had only a marginal effect on heat resistance of the C. jejuni strains in this study. A possible explanation for this effect is that rapid chilling renders C. jejuni cells unable to adapt to reduced temperatures in an active manner. This hypothesis is supported by the observation that exposure to 6°C for 24 h resulted in a significant and marked reduction in electron transport system activity when compared with controls at 37°C.

Function of Ech Hydrogenase in Ferredoxin-Dependent, Membrane-Bound Electron Transport in Methanosarcina mazei

ABSTRACT Reduced ferredoxin is an intermediate in the methylotrophic and aceticlastic pathway of methanogenesis and donates electrons to membrane-integral proteins, which transfer electrons to the heterodisulfide reductase. A ferredoxin interaction has been observed previously for the Ech hydrogenase. Here we present a detailed analysis of a Methanosarcina mazei Δech mutant which shows decreased ferredoxin-dependent membrane-bound electron transport activity, a lower growth rate, and faster substrate consumption. Evidence is presented that a second protein whose identity is unknown oxidizes reduced ferredoxin, indicating an involvement in methanogenesis from methylated C1 compounds.