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Papers by Federico Herrera

Research paper thumbnail of Inhibition of the STAT3 Protein by a Dinuclear Macrocyclic Complex

Inorganic chemistry, Jan 4, 2016

A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl s... more A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl spacers, L, was prepared, and its dinuclear copper(II) and zinc(II) complexes were used as receptors for the recognition in aqueous solution of a phosphorylated peptide derived from a sequence of the STAT3 protein. A detailed study of the acid-base behavior of L and of its complexation properties as well as of the association of the phosphorylated peptide to the receptor was carried out by potentiometry in aqueous solution at 298.2 K and I = 0.10 M in KNO3. The data revealed that the receptor forms stable associations with several protonated forms of the substrate, with constant values ranging from 3.32 to 4.25 log units. The affinity of the receptor for the phosphorylated substrate studied is higher at a pH value where the receptor is mainly in the [Cu2L](4+) form and the pY residue of the substrate is in the dianionic form (pH 6.55). These results, also supported by (31)P NMR studies, s...

Research paper thumbnail of Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin

Molecular and Cellular Endocrinology, 2016

Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antipr... more Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.

Research paper thumbnail of Daily Rhythm of Gene Expression in Rat Superoxide Dismutases

Antioxidant enzymes are a mainstay of the defense system of any organism to fight oxidative stres... more Antioxidant enzymes are a mainstay of the defense system of any organism to fight oxidative stress caused by physiological and non-physiological production of free radicals. The oxidative status of the tissues is known to regulate these enzymes, together with other factors such as hormones and cytokines. In the present work, we show the daily rhythmicity in the expression of genes for copper-zinc and manganese superoxide dismutases (Cu-Zn and Mn SODs) as observed in several tissues of normal male rats. Intestine, lung, and cerebellum showed significant daily variations. Liver, brain cortex, and mesencephalon also have daily changes although statistically not significant. A possible relation with the oxidative status and the metabolic activity of the organism is discussed.

Research paper thumbnail of Intracellular redox state regulation by parthenolide

Biochemical and Biophysical Research Communications, Jul 1, 2005

Research paper thumbnail of Melatonin: Relationship with Cell Death

Research paper thumbnail of B06 Exploring The Role Of Phosphorylation In Huntingtin Aggregation Dynamics

Journal of Neurology, Neurosurgery & Psychiatry, 2014

Research paper thumbnail of Paper: REGULATION OF ANTIOXIDANT ENZYMES: A SIGNIFICANT ROLE FOR MELATONIN

Research paper thumbnail of -Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila

Human Molecular Genetics, 2014

Research paper thumbnail of Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin

British Journal of Cancer, 2012

Research paper thumbnail of Imaging Protein Oligomerization in Neurodegeneration Using Bimolecular Fluorescence Complementation

Imaging and Spectroscopic Analysis of Living Cells: Imaging Live Cells in Health and Disease, 2012

Neurodegenerative disorders such as Alzheimer&amp... more Neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, or Prion diseases belong to a superfamily of pathologies known as protein misfolding disorders. The hallmark of these pathologies is the aberrant accumulation of specific proteins in beta sheet-rich amyloid aggregates either inside or outside cells. Current evidence suggests that oligomeric species, rather than mature protein aggregates, are the most toxic forms of the pathogenic proteins. This is due, at least in part, to their greater solubility and ability to diffuse between intracellular and extracellular compartments. Understanding how oligomerization occurs is essential for the development of new treatments for this group of diseases. Bimolecular fluorescence complementation assays (BiFC) have proved to be excellent systems to study aberrant protein-protein interactions, including those involved in neurodegenerative diseases. Here, we provide a detailed description of the rationale to develop and validate BiFC assays for the visualization of oligomeric species in living cells in the context of neurodegeneration. These systems could constitute powerful tools for the identification of genetic and pharmacological modifiers of protein misfolding and aggregation.

Research paper thumbnail of Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells

British Journal of Cancer, 2013

Research paper thumbnail of Studying the Molecular Determinants of Protein Oligomerization in Neurodegenerative Disorders by Bimolecular Fluorescence Complementation

Research paper thumbnail of Tryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disorders

The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, 2006

Research paper thumbnail of Antioxidants do not prevent acrylonitrile-induced toxicity

Research paper thumbnail of Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

International Journal of Molecular Sciences, 2013

Research paper thumbnail of Tau Enhances α-Synuclein Aggregation and Toxicity in Cellular Models of Synucleinopathy

Research paper thumbnail of Visualization of cell-to-cell transmission of mutant huntingtin oligomers

Research paper thumbnail of Melatonin induces apoptosis in human neuroblastoma cancer cells

Journal of Pineal Research, 2006

Research paper thumbnail of Glutamate induces oxidative stress not mediated by glutamate receptors or cystine transporters: protective effect of melatonin and other antioxidants

Journal of Pineal Research, 2001

Research paper thumbnail of Involvement of protein kinase C in melatonin?s oncostatic effect in C6 glioma cells

Journal of Pineal Research, 2007

Research paper thumbnail of Inhibition of the STAT3 Protein by a Dinuclear Macrocyclic Complex

Inorganic chemistry, Jan 4, 2016

A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl s... more A new diethylenetriamine-derived macrocycle bearing 2-methylpyridyl arms and containing m-xylyl spacers, L, was prepared, and its dinuclear copper(II) and zinc(II) complexes were used as receptors for the recognition in aqueous solution of a phosphorylated peptide derived from a sequence of the STAT3 protein. A detailed study of the acid-base behavior of L and of its complexation properties as well as of the association of the phosphorylated peptide to the receptor was carried out by potentiometry in aqueous solution at 298.2 K and I = 0.10 M in KNO3. The data revealed that the receptor forms stable associations with several protonated forms of the substrate, with constant values ranging from 3.32 to 4.25 log units. The affinity of the receptor for the phosphorylated substrate studied is higher at a pH value where the receptor is mainly in the [Cu2L](4+) form and the pY residue of the substrate is in the dianionic form (pH 6.55). These results, also supported by (31)P NMR studies, s...

Research paper thumbnail of Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin

Molecular and Cellular Endocrinology, 2016

Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antipr... more Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine.

Research paper thumbnail of Daily Rhythm of Gene Expression in Rat Superoxide Dismutases

Antioxidant enzymes are a mainstay of the defense system of any organism to fight oxidative stres... more Antioxidant enzymes are a mainstay of the defense system of any organism to fight oxidative stress caused by physiological and non-physiological production of free radicals. The oxidative status of the tissues is known to regulate these enzymes, together with other factors such as hormones and cytokines. In the present work, we show the daily rhythmicity in the expression of genes for copper-zinc and manganese superoxide dismutases (Cu-Zn and Mn SODs) as observed in several tissues of normal male rats. Intestine, lung, and cerebellum showed significant daily variations. Liver, brain cortex, and mesencephalon also have daily changes although statistically not significant. A possible relation with the oxidative status and the metabolic activity of the organism is discussed.

Research paper thumbnail of Intracellular redox state regulation by parthenolide

Biochemical and Biophysical Research Communications, Jul 1, 2005

Research paper thumbnail of Melatonin: Relationship with Cell Death

Research paper thumbnail of B06 Exploring The Role Of Phosphorylation In Huntingtin Aggregation Dynamics

Journal of Neurology, Neurosurgery & Psychiatry, 2014

Research paper thumbnail of Paper: REGULATION OF ANTIOXIDANT ENZYMES: A SIGNIFICANT ROLE FOR MELATONIN

Research paper thumbnail of -Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila

Human Molecular Genetics, 2014

Research paper thumbnail of Fas/Fas ligand regulation mediates cell death in human Ewing's sarcoma cells treated with melatonin

British Journal of Cancer, 2012

Research paper thumbnail of Imaging Protein Oligomerization in Neurodegeneration Using Bimolecular Fluorescence Complementation

Imaging and Spectroscopic Analysis of Living Cells: Imaging Live Cells in Health and Disease, 2012

Neurodegenerative disorders such as Alzheimer&amp... more Neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's, or Prion diseases belong to a superfamily of pathologies known as protein misfolding disorders. The hallmark of these pathologies is the aberrant accumulation of specific proteins in beta sheet-rich amyloid aggregates either inside or outside cells. Current evidence suggests that oligomeric species, rather than mature protein aggregates, are the most toxic forms of the pathogenic proteins. This is due, at least in part, to their greater solubility and ability to diffuse between intracellular and extracellular compartments. Understanding how oligomerization occurs is essential for the development of new treatments for this group of diseases. Bimolecular fluorescence complementation assays (BiFC) have proved to be excellent systems to study aberrant protein-protein interactions, including those involved in neurodegenerative diseases. Here, we provide a detailed description of the rationale to develop and validate BiFC assays for the visualization of oligomeric species in living cells in the context of neurodegeneration. These systems could constitute powerful tools for the identification of genetic and pharmacological modifiers of protein misfolding and aggregation.

Research paper thumbnail of Melatonin-induced methylation of the ABCG2/BCRP promoter as a novel mechanism to overcome multidrug resistance in brain tumour stem cells

British Journal of Cancer, 2013

Research paper thumbnail of Studying the Molecular Determinants of Protein Oligomerization in Neurodegenerative Disorders by Bimolecular Fluorescence Complementation

Research paper thumbnail of Tryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disorders

The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, 2006

Research paper thumbnail of Antioxidants do not prevent acrylonitrile-induced toxicity

Research paper thumbnail of Mechanisms Involved in the Pro-Apoptotic Effect of Melatonin in Cancer Cells

International Journal of Molecular Sciences, 2013

Research paper thumbnail of Tau Enhances α-Synuclein Aggregation and Toxicity in Cellular Models of Synucleinopathy

Research paper thumbnail of Visualization of cell-to-cell transmission of mutant huntingtin oligomers

Research paper thumbnail of Melatonin induces apoptosis in human neuroblastoma cancer cells

Journal of Pineal Research, 2006

Research paper thumbnail of Glutamate induces oxidative stress not mediated by glutamate receptors or cystine transporters: protective effect of melatonin and other antioxidants

Journal of Pineal Research, 2001

Research paper thumbnail of Involvement of protein kinase C in melatonin?s oncostatic effect in C6 glioma cells

Journal of Pineal Research, 2007