Early effects of copper accumulation on methionine metabolism

Delgado, Miguel; Pérez-Miguelsanz, Juliana; Garrido, Federico; Rodríguez-Tarduchy, Gemma; Pajares, Marı́a A.

doi:10.1007/s00018-008-8201-4

Cited by 38 publications

(52 citation statements)

References 49 publications

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“…Many liver diseases associated with impairment of methionine metabolism proceed with changes in the MAT isoenzymes that are expressed (MAT1A to MAT2A switch) (7,12,14,31,33,56,61). By this expression switch, the cell changes from high-to-low V max MAT isoenzymes with the corresponding reductions in MAT activity, AdoMet levels, and the methylation index.…”

Section: Discussionmentioning

confidence: 99%

“…Quantification of metabolite levels was performed, as previously described, at OWL Genomics Facilities (Derio, Vizcaya, Spain) (14). Briefly, tissue samples were homogenized in 0.4 M perchloric acid and the supernatant was used to determine reduced (GSH) and oxidized (GSSG) glutathione levels.…”

Section: Analysis Of Metabolite Levelsmentioning

confidence: 99%

“…Reverse transcription and PCR were done as previously described using 1.25 lg of total RNA as template and the High Capacity Archive kit (Applied Biosystems-Life Technologies, Grand Island, NY) (14). The cDNAs (10 ng) were amplified in triplicate using gene-specific primers (Supplementary Table S5) and Power SYBR Green PCR Master Mix (Applied Biosystems-Life Technologies) using the ABI 7900HT Real-Time PCR system (Applied Biosystems-Life Technologies) at the Genomic Service of the Instituto de Investigaciones Biomé-dicas ''Alberto Sols'' (CSIC-UAM).…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

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Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

Delgado

Garrido²,

Pérez-Miguelsanz³

et al. 2014

Antioxidants & Redox Signaling

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Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) a1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MATa1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MATa1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MATa1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MATa1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine-and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MATa1 subcellular distribution. Antioxid. Redox Signal. 20, 2541-2554.

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Metabolite Levelsmentioning

confidence: 99%

Section: Quantitative Rt-pcrmentioning

confidence: 99%

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Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

Delgado

Garrido²,

Pérez-Miguelsanz³

et al. 2014

Antioxidants & Redox Signaling

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“…Este aminoácido es utilizado en la síntesis de proteínas y en el ciclo de la metionina, ruta en la que se produce el principal donante de grupos metilo, la Sadenosilmetionina (SAM) [1]. El número y variedad de patologías en que se han detectado alteraciones en el ciclo de la metionina es cada día mayor, abarcando desde la cirrosis o el fallo hepático agudo [2], hasta el cáncer, el Parkinson, la sordera [3] y enfermedades raras, como la de Wilson [4].…”

Section: Discussionunclassified

“…Más recientemente hemos identificado que la unión de NADP + a la subunidad reguladora MAT aumenta su afinidad por el dímero de subunidades catalíticas MAT2. Esto hace de MAT II un hetero-trímero regulable por mecanismos redox, que también reducen drásticamente el nivel de expresión de MAT en un modelo de enfermedad de Wilson [4]. Estos datos modifican la visión clásica de la composición de MAT II, y añaden un nuevo nivel de complejidad a la regulación redox de las MATs.…”

Section: Discussionunclassified

Regulación redox del ciclo de la metionina

Pajares¹

2015

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Synthesis, structure elucidation, DNA binding and molecular docking studies of novel copper(II) complexes of two 1,3,4‐thiadiazolethiosemicarbazone derivatives

Takroni

Farghaly

Harras

et al. 2020

Applied Organom Chemis

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Four novel Cu(II) chelates were synthesized by reacting hydrated CuCl2 and Cu(CH3COO)2 with two derivatives of 1,3,4‐thiadiazolethiosemicarbazone. The structures and geometries of the synthesized complexes were deduced applying the alternative analytical and spectral tools confirming the complexes to have the formulae [(LH)Cu(Cl)]•0.5H2O, [(LH)Cu(OAc)(H2O)2]•0.5H2O, [(LCl)Cu(Cl)(H2O)2]•H2O and [(LCl)Cu(OAc)]; where LH and LCl are phenyl and p‐chlorophenyl derivatives of 1,3,4‐thiadiazolethiosemicarbazone ligands, respectively (deprotonated form). IR spectral data confirmed the coordination of the ligands to the copper center as monobasic tridentate in the thiol form. Thermal analysis, UV–Vis spectra and magnetic moment assured the geometry around the copper center to be square planar, trigonal bipyramid and octahedral which have been confirmed by the computational studies. The two ligand derivatives and their copper complexes were applied to evaluate their binding modes with SS‐DNA via UV–Vis spectral titration and viscosity measurements. The DNA‐binding constant (kb) values of the investigated derivatives were calculated and compared with ethidium bromide in order to assess their mode of binding with DNA. Moreover, docking study of these complexes was carried out to recognize the drug–DNA interactions and to calculate their binding energies.

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Early effects of copper accumulation on methionine metabolism

Cited by 38 publications

References 49 publications

Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

Regulación redox del ciclo de la metionina

Synthesis, structure elucidation, DNA binding and molecular docking studies of novel copper(II) complexes of two 1,3,4‐thiadiazolethiosemicarbazone derivatives

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