Perez D


Full name : Perez Daniel

First name : Daniel

Mail : Universidad Catolica de Chile, Neurobiologia Molecular, Santiago

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Country : Chile

Email :

Phone : 56 2 686 2721

Fax : 56 2 686 2717

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References (13)

Title : Poster: Cembranoids structureactivity relationship for protection against diisopropylfluorophosphate damage -
Author(s) : Eterovic VA , Carrasco M , Perez D , Ebrahim HY , Ferchmin PA , El Sayed KA
Ref : Biochemical Pharmacology , 97 :627 , 2015

Title : Neuroprotection Against Diisopropylfluorophosphate in Acute Hippocampal Slices - Ferchmin_2015_Neurochem.Res_40_2143
Author(s) : Ferchmin PA , Perez D , Cuadrado BL , Carrasco M , Martins AH , Eterovic VA
Ref : Neurochem Res , 40 :2143 , 2015
Abstract : Diisopropylfluorophosphate (DFP) is an irreversible inhibitor of acetylcholine esterase and a surrogate of the organophosphorus (OP) nerve agent sarin. The neurotoxicity of DFP was assessed as a reduction of population spike (PS) area elicited by synaptic stimulation in acute hippocampal slices. Two classical antidotes, atropine, and pralidoxime, and two novel antidotes, 4R-cembranotriene-diol (4R) and a caspase nine inhibitor, were tested. Atropine, pralidoxime, and 4R significantly protected when applied 30 min after DFP. The caspase inhibitor was neuroprotective when applied 5-10 min before or after DFP, suggesting that early synaptic apoptosis is responsible for the loss of PSs. It is likely that apoptosis starts at the synapses and, if antidotes are not applied, descends to the cell bodies, causing death. The acute slice is a reliable tool for mechanistic studies, and the assessment of neurotoxicity and neuroprotection with PS areas is, in general, pharmacologically congruent with in vivo results and predicts the effect of drugs in vivo. 4R was first found to be neuroprotective in slices and later we demonstrated that 4R is neuroprotective in vivo. The mechanism of neurotoxicity of OPs is not well understood, and there is a need for novel antidotes that could be discovered using acute slices.
ESTHER : Ferchmin_2015_Neurochem.Res_40_2143
PubMedSearch : Ferchmin_2015_Neurochem.Res_40_2143
PubMedID: 26438150

Title : Draft Genome Sequence of the Moderately Halophilic Bacterium Marinobacter lipolyticus Strain SM19 - Papke_2013_Genome.Announc_1_e00379
Author(s) : Papke RT , de la Haba RR , Infante-Dominguez C , Perez D , Sanchez-Porro C , Lapierre P , Ventosa A
Ref : Genome Announc , 1 : , 2013
Abstract : Marinobacter lipolyticus strain SM19, isolated from saline soil in Spain, is a moderately halophilic bacterium belonging to the class Gammaproteobacteria. Here, we report the draft genome sequence of this strain, which consists of a 4.0-Mb chromosome and which is able to produce the halophilic enzyme lipase LipBL.
ESTHER : Papke_2013_Genome.Announc_1_e00379
PubMedSearch : Papke_2013_Genome.Announc_1_e00379
PubMedID: 23814106
Gene_locus related to this paper: 9alte-r8b2n9 , 9alte-r8b4s5 , 9alte-r8ayh5 , 9alte-r8b0j8

Title : Poster: Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity -
Author(s) : Eterovic VA , Del Valle-Rodrigez A , Perez D , Carrasco M , Khanfar MA , El Sayed KA , Ferchmin PA
Ref : Biochemical Pharmacology , 86 :1233 , 2013

Title : Kinin-B2 receptor exerted neuroprotection after diisopropylfluorophosphate-induced neuronal damage - Torres-Rivera_2013_Neurosci_247C_273
Author(s) : Torres-Rivera W , Perez D , Park KY , Carrasco M , Platt MO , Eterovic VA , Ferchmin PA , Ulrich H , Martins AH
Ref : Neuroscience , 247C :273 , 2013
Abstract : The kinin-B2 receptor (B2BKR) activated by its endogenous ligand bradykinin participates in various metabolic processes including the control of arterial pressure and inflammation. Recently, functions for this receptor in brain development and protection against glutamate-provoked excitotoxicity have been proposed. Here, we report neuroprotective properties for bradykinin against organophosphate poisoning using acute hippocampal slices as an in vitro model. Following slice perfusion for 10min with diisopropylfluorophosphate (DFP) to initiate the noxious stimulus, responses of pyramidal neurons upon an electric impulse were reduced to less than 30% of control amplitudes. Effects on synaptic-elicited population spikes were reverted when preparations had been exposed to bradykinin 30min after challenging with DFP. Accordingly, bradykinin-induced population spike recovery was abolished by HOE-140, a B2BKR antagonist. However, the kinin-B1 receptor (B1BKR) agonist Lys-des-Arg9-bradykinin, inducing the phosphorylation of mitogen-activated protein kinase (MEK/MAPK) and cell death, abolished bradykinin-mediated neuroprotection, an effect, which was reverted by the ERK inhibitor PD98059. In agreement with pivotal B1BKR functions in this process, antagonism of endogenous B1BKR activity alone was enough for restoring population spike activity. On the other hand pralidoxime, an oxime, reactivating acetylcholinesterase (AChE) after organophosphate poisoning, induced population spike recovery after DFP exposure in the presence of bradykinin and Lys-des-Arg9-bradykinin. Lys-des-Arg9-bradykinin did not revert protection exerted by pralidoxime, however when instead bradykinin and Ly-des-Arg9-bradykinin were superfused together, recovery of population spikes diminished. These findings again confirm the neuroprotective feature of bradykinin, which is, diminished by its endogenous metabolites, stimulating the B1BKR, providing a novel understanding of the physiological roles of these receptors.
ESTHER : Torres-Rivera_2013_Neurosci_247C_273
PubMedSearch : Torres-Rivera_2013_Neurosci_247C_273
PubMedID: 23735753

Title : Identification of amino acids involved in the hydrolytic activity of lipase LipBL from Marinobacter lipolyticus - Perez_2012_Microbiology_158_2192
Author(s) : Perez D , Kovacic F , Wilhelm S , Jaeger KE , Garcia MT , Ventosa A , Mellado E
Ref : Microbiology , 158 :2192 , 2012
Abstract : The lipolytic enzyme family VIII currently includes only seven members but represents a group of lipolytic enzymes with interesting properties. Recently, we identified a gene encoding the family VIII lipase LipBL from the halophilic bacterium Marinobacter lipolyticus. This enzyme, like most lipolytic enzymes from family VIII, possesses two possible nucleophilic serines located in an S-X-X-K beta-lactamase motif and a G-X-S-X-G lipase motif. The serine in the S-X-X-K motif is a catalytic residue, but the role of serine within the common lipase consensus sequence G-X-S-X-G has not yet been systematically studied. Here, the previously reported time-intensive procedure for purification of recombinant LipBL was replaced by one-step metal-affinity chromatography purification in the presence of ATP. Heterologous co-expression of His(6)-tagged LipBL with the cytoplasmic molecular chaperones GroEL/GroES was necessary to obtain catalytically active LipBL. Site-directed mutagenesis performed to map the active site of LipBL revealed that mutation of serine and lysine in the beta-lactamase motif (S(72)-M-T-K(75)) to alanine abolished the enzyme activity of LipBL, in contrast to mutation of the serine in the lipase consensus motif (S321A). Furthermore, mutagenesis was performed to understand the role of the G-X-S-X-G motif and other amino acids that are conserved among family VIII esterases. We describe how mutations in the conserved G-X-S-X-G motif altered the biochemical properties and substrate specificity of LipBL. Molecular modelling results indicate the location of the G-X-S(321)-X-G motif in a loop close to the catalytic centre of LipBL, presumably representing a substrate-binding site of LipBL.
ESTHER : Perez_2012_Microbiology_158_2192
PubMedSearch : Perez_2012_Microbiology_158_2192
PubMedID: 22609754

Title : Poster: A structure-activity study of 4R-cembranoid reversal of diisopropylfluorophosphate-inflicted functional impairment in hippocampal slices -
Author(s) : del Valle-Rodriguez A , Perez D , Ferchmin PA , El Sayed KA , Eterovic VA
Ref : Biochemical Pharmacology , 82 :1032 , 2011

Title : Poster: 4R-cembratrienediol protects against diisopropylfluorophosphate-induced neurodegeneration with a long window of therapeutic opportunity -
Author(s) : Ferchmin PA , Alves JM , Perez D , Cuadrado B , Carrasco M , Roman JMV , Martins HAB , Segarra AC , Eterovic VA
Ref : Biochemical Pharmacology , 82 :1045 , 2011

Title : A novel halophilic lipase, LipBL, showing high efficiency in the production of eicosapentaenoic acid (EPA) - Perez_2011_PLoS.One_6_e23325
Author(s) : Perez D , Martin S , Fernandez-Lorente G , Filice M , Guisan JM , Ventosa A , Garcia MT , Mellado E
Ref : PLoS ONE , 6 :e23325 , 2011
Abstract : BACKGROUND: Among extremophiles, halophiles are defined as microorganisms adapted to live and thrive in diverse extreme saline environments. These extremophilic microorganisms constitute the source of a number of hydrolases with great biotechnological applications. The interest to use extremozymes from halophiles in industrial applications is their resistance to organic solvents and extreme temperatures. Marinobacter lipolyticus SM19 is a moderately halophilic bacterium, isolated previously from a saline habitat in South Spain, showing lipolytic activity. METHODS AND FINDINGS: A lipolytic enzyme from the halophilic bacterium Marinobacter lipolyticus SM19 was isolated. This enzyme, designated LipBL, was expressed in Escherichia coli. LipBL is a protein of 404 amino acids with a molecular mass of 45.3 kDa and high identity to class C beta-lactamases. LipBL was purified and biochemically characterized. The temperature for its maximal activity was 80 degrees C and the pH optimum determined at 25 degrees C was 7.0, showing optimal activity without sodium chloride, while maintaining 20% activity in a wide range of NaCl concentrations. This enzyme exhibited high activity against short-medium length acyl chain substrates, although it also hydrolyzes olive oil and fish oil. The fish oil hydrolysis using LipBL results in an enrichment of free eicosapentaenoic acid (EPA), but not docosahexaenoic acid (DHA), relative to its levels present in fish oil. For improving the stability and to be used in industrial processes LipBL was immobilized in different supports. The immobilized derivatives CNBr-activated Sepharose were highly selective towards the release of EPA versus DHA. The enzyme is also active towards different chiral and prochiral esters. Exposure of LipBL to buffer-solvent mixtures showed that the enzyme had remarkable activity and stability in all organic solvents tested. CONCLUSIONS: In this study we isolated, purified, biochemically characterized and immobilized a lipolytic enzyme from a halophilic bacterium M. lipolyticus, which constitutes an enzyme with excellent properties to be used in the food industry, in the enrichment in omega-3 PUFAs.
ESTHER : Perez_2011_PLoS.One_6_e23325
PubMedSearch : Perez_2011_PLoS.One_6_e23325
PubMedID: 21853111

Title : A cembranoid protects acute hippocampal slices against paraoxon neurotoxicity - Eterovic_2011_Toxicol.In.Vitro_25_1468
Author(s) : Eterovic VA , Perez D , Martins AH , Cuadrado BL , Carrasco M , Ferchmin PA
Ref : Toxicol In Vitro , 25 :1468 , 2011
Abstract : Many neurotoxic organophosphates (OPs) inhibit acetylcholinesterase (AChE) and as a result can cause a life threatening cholinergic crisis. Current medical countermeasures, which typically include atropine and oximes target the cholinergic crisis and are effective in decreasing mortality but do not sufficiently protect against delayed neurological deficits. There is, therefore, a need to develop neuroprotective drugs to prevent long-term neurological deficits. We used acute hippocampal slices to test the hypothesis that 4R,6R-cembratrienediol (4R) protects against functional damage caused by the OP paraoxon (POX). To assess hippocampal function, we measured synaptically evoked population spikes (PSs). Application of 4R reversed POX inhibition of PSs and the EC(50) of this effect was 0.8 muM. Atropine alone did not protect against POX neurotoxicity, but it did enhance protection by 4R. Pralidoxime partially regenerated AChE activity and protected against POX inhibition of PSs. 4R did not regenerate AChE suggesting that under our experimental conditions, the deleterious effect of POX on hippocampal function is not directly related to AChE inhibition. In conclusion, 4R is a promising neuroprotective compound against OP neurotoxins.
ESTHER : Eterovic_2011_Toxicol.In.Vitro_25_1468
PubMedSearch : Eterovic_2011_Toxicol.In.Vitro_25_1468
PubMedID: 21569834

Title : Poster: A novel nicotinic antagonist protects the function of hippocampal slices against neurotoxic organophosphates -
Author(s) : Ferchmin PA , Perez D , Martins AH , Cuadrado BL , Carrasco M , Eterovic VA
Ref : Biochemical Pharmacology , 78 :904 , 2009

Title : Molecular Interactions of Acetylcholinesterase with the Synaptic Basal Lamina and the Senile Plaques -
Author(s) : Inestrosa NC , Alarcon R , Alvarez A , Calderon FH , Campos EO , Casanueva OI , De Ferrari GV , Deprez P , Garcia-Huidobro T , Munoz FJ , Perez D , Reyes AE
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :167 , 1998

Title : Kinetic and thermodynamic effects of acetylcholinesterase on the solubility of Abeta peptide -
Author(s) : Perez D , Alarcon R , Inestrosa NC
Ref : Journal de Physiologie (Paris) , 92 :479 , 1998