Fernandez V

References (5)

Title : Increase of carboxylesterase activity in Fasciola hepatica recovered from triclabendazole treated sheep - Scarcella_2012_Mol.Biochem.Parasitol_185_151
Author(s) : Scarcella S , Miranda-Miranda E , Cossio-Bayugar R , Ceballos L , Fernandez V , Solana H
Ref : Molecular & Biochemical Parasitology , 185 :151 , 2012
Abstract : In the present work we evaluate in vivo the activity of carboxylesterase of Fasciola hepatica exposed to triclabendazole We observed a statistically significant increase in enzyme activity at 24 and 48h post treatment P<0.01 and P<0.001 respectively The zymogram of cytosolic fractions identified a protein of 170kDa containing the carboxylesterase activity The densitograms of the zymograms confirmed the phenomenon of enzyme induction under the experimental conditions of the assay These results provide not only the understanding of the importance of this metabolic pathway in flukes but carboxylesterase would also be an enzyme that could participate more actively in the development of anthelmintic resistance at TCBZ.
ESTHER : Scarcella_2012_Mol.Biochem.Parasitol_185_151
PubMedSearch : Scarcella_2012_Mol.Biochem.Parasitol_185_151
PubMedID: 22814337

Title : Probe Development Efforts to Identify Novel Inhibitors of Protein Phosphatase Methylesterase-1 (PME-1) - Bachovchin_2010_Probe.Report__1
Author(s) : Bachovchin DA , Speers AE , Brown SJ , Spicer TP , Fernandez V , Ferguson J , Mohr JT , Murphy J , Fu GC , Cravatt BF , Hodder PS , Rosen H
Ref : Probe Report , : , 2010
Abstract : Reversible protein phosphorylation networks play essential roles in most cellular processes. While over 500 kinases catalyze protein phosphorylation, only two enzymes, PP1 and PP2A, are responsible for more than 90% of all serine/threonine phosphatase activity. Phosphatases, unlike kinases, achieve substrate specificity through complex subunit assembly and post-translational modifications rather than number. Mutations in several of the PP2A subunits have been identified in human cancers, suggesting that PP2A may act as a tumor suppressor. Adding further complexity, several residues of the catalytic subunit of PP2A can be reversibly phosphorylated, and the C-terminal leucine residue can be reversibly methylated. Protein phosphatase methylesterase-1 (PME-1) is specifically responsible for demethylation of the carboxyl terminus. Methylesterification is thought to control the binding of different subunits to PP2A, but little is known about physiological significance of this post-translational modification in vivo. Recently, PME-1 has been identified as a protector of sustained ERK pathway activity in malignant gliomas. PME-1 knockout mice generated by targeted gene disruption result in perinatal lethality, underscoring the importance of PME-1 but hindering biological studies. The Scripps Research Institute Molecular Screening Center (SRIMSC), part of the Molecular Libraries Probe Production Centers Network (MLPCN), identified a potent and selective PME-1 inhibitor probe, ML174, by high-throughput screening using fluorescence polarization-activity-based protein profiling (FluoPol-ABPP). ML174, with an IC50 of 10 nM, is based on the aza-beta-lactam scaffold and is selective for PME-1 among serine hydrolases in human cell line proteomes as assessed by gel-based competitive-activity-based protein profiling. Among more than 30 serine hydrolase anti-targets, ML174 is selective at 1 muM. Additionally, ML174 was shown in situ to be highly active against PME-1 and to result in 85% reduction of demethylated PP2A. We previously reported a modestly potent 500 nM inhibitor that was selective for PME-1, the first reported selective PME-1 inhibitor. ML174 is 50 times more potent and from an entirely different structural and mechanistic class of inhibitors. Due to its much higher potency, ML174 has greater potential for use in long time-course in situ studies, and is a much better candidate for in vivo applications.
ESTHER : Bachovchin_2010_Probe.Report__1
PubMedSearch : Bachovchin_2010_Probe.Report__1
PubMedID: 22834039

Title : Probe Report for PME-1 Inhibitors - Bachovchin_2010_Probe.Report__2
Author(s) : Bachovchin DA , Speers AE , Zuhl AM , Brown SJ , Cravatt BF , Fernandez V , Spicer T , Mercer BA , Ferguson J , Hodder P , Rosen HR
Ref : Probe Report , : , 2010
Abstract : Recent findings have identified protein phosphatase methylesterase-1 (PME-1) as a protector of sustained ERK pathway activity in malignant gliomas. PME-1 is a protein methylesterase that functions in the regulation of protein phosphatase 2A (PP2A) by reversible methylation. Biochemical elucidation of PME-1 would thus greatly benefit from the development of potent and selective chemical inhibitors. The probe compound ML136 (CID-44607965), containing a sulfonyl acrylonitrile core, represents the first potent, selective inhibitor of PME-1. Moreover, the probe does not appear to exhibit cytotoxicity. Thus, ML136 should serve as a useful tool for in vitro and in situ research assays in which it is desirable to specifically block PME-1 activity.
ESTHER : Bachovchin_2010_Probe.Report__2
PubMedSearch : Bachovchin_2010_Probe.Report__2
PubMedID: 21433379

Title : Vitamin E but not 17beta-estradiol protects against vascular toxicity induced by beta-amyloid wild type and the Dutch amyloid variant - Munoz_2002_J.Neurosci_22_3081
Author(s) : Munoz FJ , Opazo C , Gil-Gomez G , Tapia G , Fernandez V , Valverde MA , Inestrosa NC
Ref : Journal of Neuroscience , 22 :3081 , 2002
Abstract : Amyloid beta-peptide (Abeta) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Abeta yielding Abeta(Glu22-->Gln). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Abeta(1-40 Glu22-->Gln) and Abeta(1-40 wild-type) fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that Abeta(Glu22-->Gln) fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Abeta(1-40 wild-type)-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17beta-estradiol on vascular damage induced by Abeta(wild-type) and Abeta(Glu22-->Gln). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells, although 17beta-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils.
ESTHER : Munoz_2002_J.Neurosci_22_3081
PubMedSearch : Munoz_2002_J.Neurosci_22_3081
PubMedID: 11943811

Title : PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase-amyloid complexes, amyloid25-35 fragment, glutamate, and hydrogen peroxide - Calderon_1999_J.Neurosci.Res_56_620
Author(s) : Calderon FH , Bonnefont A , Munoz FJ , Fernandez V , Videla LA , Inestrosa NC
Ref : Journal of Neuroscience Research , 56 :620 , 1999
Abstract : This work addresses the differential effects of several oxidative insults on two neuronal cell lines, PC12 and Neuro 2a cells, extensively used as neuronal models in vitro. We measured cellular damage using the cytotoxic assays for MTT reduction and LDH release and found that acetylcholinesterase (AChE)-amyloid-beta-peptide (Abeta) complexes, Abeta25-35 fragment, glutamate and H2O2 were over 200-fold more toxic to PC12 than to Neuro 2a cells. 17alpha and 17beta estradiol were able to protect both cell types from damage caused by H2O2 or glutamate. By contrast, other insults not related to oxidative stress, such as those caused by the nonionic detergent Triton X-100 and serum deprivation, induced a similar level of damage in both PC12 and Neuro 2a cells. Considering that the Abeta peptide, H2O2 and glutamate are cellular insults that cause an increase in reactive oxygen species (ROS), the intracellular levels of the antioxidant compound, glutathione were verified. Neuro 2a cells were found to have 4- to 5-fold more glutathione than PC12 cells. Our results suggest that Neuro 2a cells are less susceptible to exposure to AChE-Abeta complexes, Abeta25-35 fragment, glutamate and H2O2 than PC12 cells, due to higher intracellular levels of antioxidant defense factors.
ESTHER : Calderon_1999_J.Neurosci.Res_56_620
PubMedSearch : Calderon_1999_J.Neurosci.Res_56_620
PubMedID: 10374817