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Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360852


Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.

Antidepressivos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Fluoxetina/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Animais , Ácidos Graxos Insaturados/metabolismo , Macaca mulatta , Masculino
Biomolecules ; 11(5)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064997


Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.

Antipsicóticos/efeitos adversos , Sintomas Comportamentais/epidemiologia , Biomarcadores/sangue , Lipidômica/métodos , Esquizofrenia/tratamento farmacológico , Triglicerídeos/sangue , Adolescente , Adulto , Sintomas Comportamentais/sangue , Sintomas Comportamentais/induzido quimicamente , Sintomas Comportamentais/diagnóstico , Feminino , Humanos , Pacientes Internados/psicologia , Pacientes Internados/estatística & dados numéricos , Masculino , Federação Russa/epidemiologia , Esquizofrenia/patologia , Resultado do Tratamento , Adulto Jovem
BMC Genomics ; 21(1): 331, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349672


BACKGROUND: Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today. RESULTS: We annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana. Differential expression analysis verified by proteomics identified salivary cell-specific gene expression, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants have been found to be expressed not only in salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis. CONCLUSIONS: Here we report a genome draft of Hirudo medicinalis and describe identification of novel salivary proteins and new homologs of genes encoding known anticoagulants in transcriptomes of three medicinal leech species. Our data provide new insights in genetics of blood-feeding lifestyle in leeches.

Genoma , Hirudo medicinalis/genética , Proteínas e Peptídeos Salivares/genética , Animais , Anticoagulantes/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hirudo medicinalis/metabolismo , Sanguessugas/classificação , Sanguessugas/genética , Sanguessugas/metabolismo , Proteômica , Saliva/metabolismo , Proteínas e Peptídeos Salivares/metabolismo
Nucleic Acids Res ; 46(17): 8966-8977, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30102362


Several studies have described functional peptides encoded in RNA that are considered to be noncoding. Telomerase RNA together with telomerase reverse transcriptase and regulatory proteins make up the telomerase complex, the major component of the telomere length-maintaining machinery. In contrast to protein subunits, telomerase RNA is expressed constitutively in most somatic cells where telomerase reverse transcriptase is absent. We show here that the transcript of human telomerase RNA codes a 121 amino acid protein (hTERP). The existence of hTERP was shown by immunoblotting, immunofluorescence microscopy and mass spectroscopy. Gain-of-function and loss-of-function experiments showed that hTERP protects cells from drug-induced apoptosis and participates in the processing of autophagosome. We suggest that hTERP regulates crosstalk between autophagy and apoptosis and is involved in cellular adaptation under stress conditions.

Adaptação Fisiológica/genética , Apoptose/genética , Autofagia/genética , RNA Mensageiro/genética , RNA/genética , Telomerase/genética , Telômero/metabolismo , Sequência de Aminoácidos , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Autofagia/efeitos dos fármacos , Gatos , Linhagem Celular Tumoral , Clonagem Molecular , Doxorrubicina/farmacologia , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Células HEK293 , Cavalos , Humanos , Células Jurkat , Camundongos , RNA/metabolismo , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Estresse Fisiológico , Telomerase/metabolismo , Telômero/química , Homeostase do Telômero
Data Brief ; 16: 700-704, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29541667


The data reported is a large-scale untargeted proteome profile for Mycoplasma gallisepticum - a model organism for studying both regulation in genome-reduced bacteria and intracellular infection (Mazin et al., 2014) [1,2]. While seminal whole-proteome studies were performed on Mycoplasma genitalium [3] and a few proteome datasets are available for Mycoplasma pneumoniae, no data-independent (DIA) proteome profiling has been published for bacteria of Mycoplasma genus. Since DIA-based proteome profiling allows to extract evidence on presence and quantity of any protein of interest in a post-acquisition manner and the data presented is describing a model which is suitable to study both proteome regulation in general and details of mycoplasma infection process [4], the proteome profiling data presented here is of value for deep annotation. The data was deposited to the PRIDE repository (PXD008198).

Sci Rep ; 7(1): 14534, 2017 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-29109403


Sea anemones (Actiniaria) are intensely popular objects of study in venomics. Order Actiniaria includes more than 1,000 species, thus presenting almost unlimited opportunities for the discovery of novel biologically active molecules. The venoms of cold-water sea anemones are studied far less than the venoms of tropical sea anemones. In this work, we analysed the molecular venom composition of the cold-water sea anemone Cnidopus japonicus. Two sets of NGS data from two species revealed molecules belonging to a variety of structural classes, including neurotoxins, toxin-like molecules, linear polypeptides (Cys-free), enzymes, and cytolytics. High-throughput proteomic analyses identified 27 compounds that were present in the venoms. Some of the toxin-like polypeptides exhibited novel Cys frameworks. To characterise their function in the venom, we heterologously expressed 3 polypeptides with unusual Cys frameworks (designated CjTL7, CjTL8, and AnmTx Cj 1c-1) in E. coli. Toxicity tests revealed that the CjTL8 polypeptide displays strong crustacean-specific toxicity, while AnmTx Cj 1c-1 is toxic to both crustaceans and insects. Thus, an improved NGS data analysis algorithm assisted in the identification of toxins with unusual Cys frameworks showing no homology according to BLAST. Our study shows the advantage of combining omics analysis with functional tests for active polypeptide discovery.

Venenos de Cnidários/química , Peptídeos/isolamento & purificação , Anêmonas-do-Mar , Animais , Venenos de Cnidários/genética , Peptídeos/análise , Anêmonas-do-Mar/química , Anêmonas-do-Mar/genética , Alinhamento de Sequência