Nitric Oxide Promotes Survival of Cerebral Cortex Neurons with Simultaneous Addition of [Fe(II)(β-Citryl-L-glutamate)] Complex in Primary Culture

Abstract

It has been reported that the activity of mitochondrial aconitase (m-aconitase) is rapidly inhibited in a variety of cells when exposed to nitric oxide (NO).NO is a free radical produced by a wide variety of cell types, that reacts predominantly with Fe(III) or Fe(II) ions of heme proteins and Fe-S centers, as well as molecular oxygen, and superoxide anion. 4,5) Moreover, NO easily reaches mitochondria from cytosolic or extracellular sources, due to its low molecular radius and hydrophobic nature.6) It has also been reported that induction of NO synthesis or exposure of different cell types to NO-donors resulted in early loss of mitochondrial aconitase (m-aconitase) activity. 1)NO-mediated inactivation of m-aconitase has been reported in a variety of cells including macrophages, 7) fibroblasts, 8) tumor cells, 9,10) and Escherichia (E.) coli, 11) though results from in vitro studies are somewhat contradictory. Indeed, in vitro studies that used porcine heart m-aconitase found that low concentrations of NO did not inactivate aconitase, whereas high concentrations led to moderate inhibition.12) Resistance of purified E. coli aconitase and human recombinant cytosolic aconitase (c-aconitase) to NO-dependent inactivation has also been reported. 13) On the contrary, inactivation by either NO or a NO-donor was reported for both m-aconitase and c-aconitase in the presence and absence of a substrate. 14)In agreement with those findings, it was shown that the active form [4Fe-4S] of m-aconitase is rapidly and directly oxidized by ONOO − , to [3Fe-4S], causing a loss of catalytic activity. 12)Another report 11) also noted that E. coli aconitase is highly sensitive to NO-mediated inactivation apparently independent of ONOO − formation. Recently, it was also reported that NO binds to Fe a in the [4Fe-4S] cluster of recombinant porcine maconitase and slowly promotes complete cluster disassembly. 6)The present findings demonstrate that NO-donors promote Fe-dependent activation of m-aconitase ([3Fe-4S] form) in vitro. In intact mitochondria, the NO-donors also promoted Fe-dependent reactivation of the enzyme disassembled by ammonium peroxodisulfate (APS). In mixed neuronal and

Untargeted Metabolomics Analysis Reveals a Link between ETHE1-Mediated Disruptive Redox State and Altered Metabolic Regulation

“…BCG was first identified in newborn rats and thought to play a role during brain development, and enzymes synthesizing and degrading BCG were recently described . During brain development, iron concentration should be tightly regulated, and it has recently been demonstrated that BCG acts as an iron carrier to activate aconitase. , The BCG concentration has been found to be elevated during growth and differentiation of neurons and during anaerobic metabolism in rats, and its iron-binding capacity suggests that BCG may enhance cell viability and accelerate mitochondrial activities through the direct transfer of iron to aconitase (Figure ).…”

1H NMR Metabolic Profiling of Earthworm (Eisenia fetida) Coelomic Fluid, Coelomocytes, and Tissue: Identification of a New Metabolite—Malylglutamate

“… 40 , 41 β-Citrylglutamate may act as a chaperone for iron to aconitase and protective complex against NO-induced aconitase inhibition. 42 , 43 Malylglutamate may form similar complexes to aid biochemical processes or protect the worm against metal burdens. The physiological functions of malylglutamate need further exploration to understand its unique presence and abundance in earthworms.…”