The overexpression of NADPH-producing enzymes counters the oxidative stress evoked by gallium, an iron mimetic

Abstract

Gallium (Ga), an iron (Fe) mimetic promoted an oxidative environment and elicited an antioxidative response in Pseudomonas fluorescens. Ga-stressed P. fluorescens was characterized by higher amounts of oxidized lipids and proteins compared to control cells. The oxidative environment provoked by Ga was nullified by increased synthesis of NADPH. The activity and expression glucose 6-phosphate dehydrogenase (G6PDH) and isocitrate dehydrogenase-NADP (ICDH) were stimulated in Ga-cultures. The induction of isoenzymes of these dehydrogenases was also evident in the Ga-stressed cells. Although superoxide dismutase (SOD) activity was significantly enhanced in Ga-stressed cultures, catalase activity experienced a marked diminution. Fe metabolism appeared to be severely impeded by Ga toxicity. This is the first demonstration of the oxidative stress evoked by Ga to be neutralized by a reductive environment generated via the overexpression of NADPH-producing enzymes.

Involvement of Fumarase C and NADH Oxidase in Metabolic Adaptation ofPseudomonas fluorescensCells Evoked by Aluminum and Gallium Toxicity

“…ROS molecules have been implicated in disrupting the activity of ACN by dismantling the Fe-S cluster (8). In addition, we have recently shown that both Al and Ga can promote oxidative stress in P. fluorescens (3,31). Thus, Al and Ga may produce an oxidative and Fe-starved environment, leading to a decrease in ACN activity.…”

“…Labile Fe can participate in the formation of ROS since this redox-active metal can donate and accept electrons. Previous work in our laboratory has shown that P. fluorescens cells exposed to either Al or Ga upregulate several antioxidant enzymes such as catalase and superoxide dismutase in order to cope with the pro-oxidant properties of these metals (3,31). In addition, enzymes involved in the production of NADPH display a generous increase in activity following exposure to either Al or Ga (17).…”

“…Toxic metals such as Ga and Al have also been implicated in the disruption of Fe-proteins (22,36). Because these two trivalent metals have atomic properties similar to those of Fe, they readily compete for Fe binding sites in proteins (3). Al has been widely regarded as a toxic mimetic of Fe.…”

Metallomics related to gallium compounds: biochemical and xenobiochemical aspects

“…The ability of gallium to trigger an oxidative environment was revealed by other studies that demonstrated an overexpression of glucose-6-phosphate dehydrogenase and isocitrate dehydrogenase-NADPH, two NADPH producing enzymes. Also, catalase activity was shown to be diminished, Fe metabolism being severely braked by Ga toxicity [47]. A series of [Ga(LX) 2 ]ClO 4 compounds ((LX) -= deprotonated form of ligands containing pyridine and 4,6-substituted phenol moieties with X = methoxy, nitro, chloro, bromo, and iodo) displayed growth-inhibition activity on cisplatin-resistant human neuroblastoma cells [48,49].…”

Inorganic Nanoparticles: Innovative Tools for Antimicrobial Agents

“…IncreasedproductionofH 2 O 2 was noticed due to Ga 3+ antibacterial action [51].However, Ga 3+ quenches the superoxide ion signal [51],anditisnotyetclearwhethertheROSsare the main reason or only a consequence of the Ga 3+ antibacterial action.…”