.BETA.-Citryl-L-glutamate Acts as an Iron Carrier to Activate Aconitase Activity

Hamada-Kanazawa, Michiko; Narahara, Masanori; Takano, Masaoki; Min, Kyong Son; Tanaka, Keiichi; Miyake, Masanobu

doi:10.1248/bpb.34.1455

Cited by 17 publications

(21 citation statements)

References 35 publications

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“…4d, [Fe(II)(β-CG)] promoted dose-dependently aconitase-activation in the presence of SIN (1 mm), while it activated that only moderately without SIN as previously described. 16) These findings suggest that NO essentially requires Fe(II) ion for binding to itself for aconitase-activation.…”

Section: Comparison Of Effects Of Nitroprusside With Those Of Other Imentioning

confidence: 95%

“…15) [Fe(II)(Citrate)] complex were prepared from Fe(II) O and trisodium citrate as previously described. 16) All other reagents were purchased from commercial sources at the highest grade available.…”

Section: Methodsmentioning

confidence: 99%

“…After incubation, 30-µL aliquots of the reaction mixtures were suspended in 30 µL of 1% Triton X-100, and solubilized, then 50-µL aliquots were used for determination of aconitase activity. 16) Primary Cell Cultures from Newborn Mouse Brain Tissues Cerebrums of 1-d-old ddY mice were dissected and placed in Ca 2+ /Mg 2+ -free dulbecco's phosphate-buffered saline [PBS(−)]. dissociation and cultures of neurons were performed as previously described, 18) with slight modifications.…”

Section: Methodsmentioning

confidence: 99%

“…16) In brief, 2×10 6 cells were cultured in 24-well plates for 3 d, then solubilized in 1 mL of lysis buffer, and treated with a proteinase K and RNase A solution. dNA was extracted twice with phenolchloroform and precipitated twice, first with isopropyl alcohol and then with 70% ethanol, after which air-dried pellets were solubilized.…”

Section: Methodsmentioning

confidence: 99%

“…4C Recently, we found that β-citrylglutamate (β-CG), isolated from newborn rat brains, was an endogenous low molecular weight Fe chelator, 36) while the [Fe(II)(β-CG)] complex plays a role as an Fe-carrier for mitochondrial aconitase, and then activates it. 16) Therefore, we used the[Fe(II)(β-CG)] complex as an Fe-complex containing moderately bound Fe in our experiments. As shown in Fig.…”

Section: Comparison Of Effects Of Nitroprusside With Those Of Other Imentioning

confidence: 99%

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

Hamada-Kanazawa

Narahara

Takano

et al. 2013

Biological & Pharmaceutical Bulletin

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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

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Section: Comparison Of Effects Of Nitroprusside With Those Of Other Imentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Comparison Of Effects Of Nitroprusside With Those Of Other Imentioning

confidence: 99%

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

Hamada-Kanazawa

Narahara

Takano

et al. 2013

Biological & Pharmaceutical Bulletin

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Metabolomic and lipidomic signatures in autosomal dominant and late‐onset Alzheimer's disease brains

Novotny

Fernández

Wang

et al. 2022

Alzheimer's & Dementia

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Introduction:The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. Methods:We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE ɛ4, and TREM2 risk variant carriers, and sporadic AD (sAD). Results:We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration.Discussion: AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation.

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Defining the landscape of metabolic dysregulations in cancer metastasis

Kader

Dib

Achkar

et al. 2021

Clin Exp Metastasis

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Metastasis is the primary cause of cancer related deaths due to the limited number of efficient druggable targets. Signatures of dysregulated cancer metabolism could serve as a roadmap for the determination of new treatment strategies. However, the metabolic signatures of metastatic cells remain vastly elusive. Our aim was to determine metabolic dysregulations associated with high metastatic potential in breast cancer cell lines. We have selected 5 triple negative breast cancer (TNBC) cell lines including three with high metastatic potential (HMP) (MDA-MB-231, MDA-MB-436, MDA-MB-468) and two with low metastatic potential (LMP) (BT549, HCC1143). The normal epithelial breast cell line (hTERT-HME1) was also investigated. The untargeted metabolic profiling of cells and growth media was conducted and total of 479 metabolites were quantified. First we characterized metabolic features differentiating TNBC cell lines from normal cells as well as identified cell line specific metabolic fingerprints. Next, we determined 92 metabolites in cells and 22 in growth medium that display significant differences between LMP and HMP. The HMP cell lines had elevated level of molecules involved in glycolysis, TCA cycle and lipid metabolism. We identified metabolic advantages of cell lines with HMP beyond enhanced glycolysis by pinpointing the role of branched chain amino acids (BCAA) catabolism as well as molecules supporting coagulation and platelet activation as important contributors to the metastatic cascade. The landscape of metabolic dysregulations, characterized in our study, could serve as a roadmap for the identification of treatment strategies targeting cancer cells with enhanced metastatic potential.

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.BETA.-Citryl-L-glutamate Acts as an Iron Carrier to Activate Aconitase Activity

Cited by 17 publications

References 35 publications

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

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

Metabolomic and lipidomic signatures in autosomal dominant and late‐onset Alzheimer's disease brains

Defining the landscape of metabolic dysregulations in cancer metastasis

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