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1.
Zhonghua Gan Zang Bing Za Zhi ; 29(5): 484-487, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34107591

RESUMO

Chronic liver diseases caused by a variety of causes can lead to the formation of liver fibrosis, and further develop into liver cirrhosis, which is a serious threat to human life and health. As a new research field, lipidomics has been developing vigorously in recent years and has shown great potential in the field of liver fibrosis research. This article introduces lipidomics technology, and discusses its pathogenesis, lipotoxicity biomarkers and emerging therapeutic targets, so as to provide a prospects for the future development of lipidomics in the field of liver fibrosis.


Assuntos
Lipidômica , Hepatopatias , Biomarcadores , Humanos , Metabolismo dos Lipídeos , Cirrose Hepática
2.
ACS Chem Neurosci ; 12(12): 2122-2132, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34085811

RESUMO

Fermented soybean lipids (FSE-C) is an extract enriched in active lipid classes. To explore whether FSE-C can alleviate cognitive damage triggered by the exposure to microwave radiation through regulating lipid metabolism, we employed lipidomic profiling based on a UPLC-MS to investigate differential lipid metabolites in the serum and hippocampus of rats. The results showed that orally administered FSE-C could protect from cognitive damage in microwave-induced rats. Serum lipidomics indicated that FSE-C effectively facilitated the recovery of 43 differential lipid metabolites including 6 phosphatidylcholines (PCs), 5 phosphatidylethanolamines (PEs), 1 phosphatidylinositol, 3 lysophosphatidylcholines (LPCs), 6 lysophosphatidylethanolamines (LPEs), and 22 triglycerides (TGs), which was consistent with the analysis of serum TG levels. Moreover, FSE-C positively coordinated hexacosanoic acid, 2 PCs, 4 sphingomyelins (SMs), and 11 TGs, through the hippocampal lipidomics. Collectively, these findings suggested that phospholipid and TG metabolisms were significantly modified in microwave-exposed rats. TGs may be regarded as potential biomarkers to further investigate and evaluate the roles and functions of FSE-C on the attenuation of cognitive damage induced by microwave radiation.


Assuntos
Alimentos e Bebidas Fermentados , Lipidômica , Animais , Cromatografia Líquida , Cognição , Hipocampo , Metabolismo dos Lipídeos , Micro-Ondas , Ratos , Soja , Espectrometria de Massas em Tandem
3.
BMJ Open ; 11(5): e043644, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958336

RESUMO

INTRODUCTION: We describe the rationale and broad study design of the Indian Diabetes and Metabolic Health (InDiMeT) study, a new prospective, observational study incorporating extensive epigenetic (DNA methylation) and lipidomic signatures to examine their association with the dysregulation of adipose de novo lipogenesis (DNL) in South Asian Indians. The InDiMeT study aims to use a case-control design to identify genetic and modifiable-environmental-lifestyle associated determinants of (1) epigenomic (DNA methylome) dysregulation of adipose DNL in type 2 diabetes mellitus (T2DM) adipose tissue, (2) identify correlates of epigenomic (DNA methylome) dysregulation of adipose DNL in peripheral blood mononuclear cells (PBMCs) from T2DM subjects and (3) elucidate plasma lipidomic correlates of adipose DNL in T2DM that can be used as biomarkers of adipose tissue dysfunction. METHODS AND ANALYSIS: The InDiMeT study will involve recruitment of 176 normoglycaemic and T2DM individuals who will be undergoing laparoscopic surgery for clinical conditions. Extensive phenotyping of the subjects will be conducted and DNA methylome and lipidomic measurements will be made. The adipose DNL pathway genes are likely to be hypermethylated in patients with T2DM with corresponding reduction of gene expression. Correlates of epigenomic (DNA methylome) dysregulation of adipose DNL pathway in PBMCs and their adipose and plasma lipidomic signatures in T2DM subjects could act as early markers of development of T2DM. ETHICS AND DISSEMINATION: For the InDiMeT study, ethical approval for addressing the specific aims has been obtained from the Institutional Ethics Committee, St John's Medical College and Hospital, St John's National Academy of Health Sciences, Bangalore. Findings from this study will be disseminated through scientific publications in peer-reviewed journals, research conferences and via presentations to stakeholders, patients, clinicians, public and policymakers through appropriate channels.


Assuntos
Diabetes Mellitus Tipo 2 , Tecido Adiposo , Diabetes Mellitus Tipo 2/genética , Epigênese Genética , Epigenômica , Homeostase , Humanos , Índia , Leucócitos Mononucleares , Lipidômica , Estudos Observacionais como Assunto , Estudos Prospectivos
4.
Nat Commun ; 12(1): 2813, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001876

RESUMO

Apicomplexa are obligate intracellular parasites responsible for major human diseases. Their intracellular survival relies on intense lipid synthesis, which fuels membrane biogenesis. Parasite lipids are generated as an essential combination of fatty acids scavenged from the host and de novo synthesized within the parasite apicoplast. The molecular and metabolic mechanisms allowing regulation and channeling of these fatty acid fluxes for intracellular parasite survival are currently unknown. Here, we identify an essential phosphatidic acid phosphatase in Toxoplasma gondii, TgLIPIN, as the central metabolic nexus responsible for controlled lipid synthesis sustaining parasite development. Lipidomics reveal that TgLIPIN controls the synthesis of diacylglycerol and levels of phosphatidic acid that regulates the fine balance of lipids between storage and membrane biogenesis. Using fluxomic approaches, we uncover the first parasite host-scavenged lipidome and show that TgLIPIN prevents parasite death by 'lipotoxicity' through effective channeling of host-scavenged fatty acids to storage triacylglycerols and membrane phospholipids.


Assuntos
Membrana Celular/metabolismo , Lipidômica/métodos , Fosfatidato Fosfatase/metabolismo , Fosfolipídeos/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Células Cultivadas , Citoplasma/metabolismo , Retículo Endoplasmático/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/parasitologia , Prepúcio do Pênis/citologia , Técnicas de Silenciamento de Genes , Homeostase/genética , Interações Hospedeiro-Parasita , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Fosfatidato Fosfatase/genética , Proteínas de Protozoários/genética , Toxoplasma/genética , Toxoplasma/ultraestrutura
5.
Nat Commun ; 12(1): 2869, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001877

RESUMO

Single-cell analysis is critical to revealing cell-to-cell heterogeneity that would otherwise be lost in ensemble analysis. Detailed lipidome characterization for single cells is still far from mature, especially when considering the highly complex structural diversity of lipids and the limited sample amounts available from a single cell. We report the development of a general strategy enabling single-cell lipidomic analysis with high structural specificity. Cell fixation is applied to retain lipids in the cell during batch treatments prior to single-cell analysis. In addition to tandem mass spectrometry analysis revealing the class and fatty acyl-chain for lipids, batch photochemical derivatization and single-cell droplet treatment are performed to identify the C=C locations and sn-positions of lipids, respectively. Electro-migration combined with droplet-assisted electrospray ionization enables single-cell mass spectrometry analysis with easy operation but high efficiency in sample usage. Four subtypes of human breast cancer cells are correctly classified through quantitative analysis of lipid C=C location or sn-position isomers in ~160 cells. Most importantly, the single-cell deep lipidomics strategy successfully discriminates gefitinib-resistant cells from a population of wild-type human lung cancer cells (HCC827), highlighting its unique capability to promote precision medicine.


Assuntos
Lipidômica/métodos , Lipídeos/análise , Análise de Célula Única/métodos , Espectrometria de Massas em Tandem/métodos , Linhagem Celular Tumoral , Ésteres do Colesterol/análise , Ésteres do Colesterol/química , Diglicerídeos/análise , Diglicerídeos/química , Ácidos Graxos/análise , Ácidos Graxos/química , Humanos , Isomerismo , Lipídeos/química , Células MCF-7 , Estrutura Molecular , Reprodutibilidade dos Testes , Triglicerídeos/análise , Triglicerídeos/química
6.
J Agric Food Chem ; 69(18): 5372-5380, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33939412

RESUMO

Arsenic ions (As3+) have been recognized as a hazard that threatens the health of humans. Metallothionein (MT) rich in cysteine may provide favorable binding sites for chelation of As3+. However, the influence of MT on As3+-induced toxicity and the underlying mechanism are poorly understood, especially at the metabolic level. Herein, the effects of MT on As3+-induced toxicity were evaluated. Cell viability analysis suggested that MT alleviated As3+-induced cytotoxicity. The metabolic response of PC12 cells to As3+ investigated by lipidomics and metabolomics indicated that the presence of As3+ disrupted phospholipids metabolism and induced cell membrane damage. Moreover, energy and amino acid metabolism were perturbed by As3+. The perturbation of As3+ on metabolism was further illustrated by the decrease of the mitochondrial membrane potential and the rise of cellular reactive oxygen species (ROS). On the contrary, MT rescued As3+-induced metabolic disorder and suppressed ROS accumulation. In addition, the binding process between As3+ and MT was characterized. The results proved that the As3+-MT complex was formed and chelated As3+-scavenged ROS, thus alleviating the toxic effects of As3+. These results revealed that MT would be a potential agent to reduce As3+-induced cytotoxicity.


Assuntos
Arsênio , Metalotioneína , Animais , Arsênio/toxicidade , Humanos , Lipidômica , Metabolômica , Metalotioneína/genética , Ratos , Espécies Reativas de Oxigênio
7.
Talanta ; 231: 122367, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33965032

RESUMO

The lipidomic research is currently devoting considerable effort to the harmonization that should enable the generation of comparable and accurate quantitative lipidomic data across different laboratories and regardless of the mass spectrometry-based platform used. In the present study, we systematically investigate the effects of the experimental setup on quantitative lipidomics data obtained by two lipid class separation approaches, hydrophilic interaction liquid chromatography (HILIC) and ultrahigh-performance supercritical fluid chromatography (UHPSFC), coupled to two different quadrupole - time of flight (QTOF) mass spectrometers from the same vendor. This approach is applied for measurements of 268 human plasma samples of healthy volunteers and renal cell carcinoma patients resulting in four data sets. We investigate and visualize differences among these data sets by multivariate data analysis methods, such as principal component analysis (PCA), orthogonal partial least square discriminant analysis (OPLS-DA), box plots, and logarithmic correlations of molar concentrations of individual lipid species. The results indicate that even measurements in the same laboratory for the same samples using different analytical platforms may yield slight variations in the molar concentrations determined. The normalization to a reference sample with defined lipid concentrations can further diminish these small differences, resulting in highly homogenous molar concentrations of individual lipid species. This strategy indicates a potential approach towards the reporting of comparable quantitative results independent from the quantitative approach and mass spectrometer used, which is important for a wider acceptance of lipidomics data in various biomarker inter-laboratory studies and ring trials.


Assuntos
Cromatografia com Fluido Supercrítico , Lipidômica , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Interações Hidrofóbicas e Hidrofílicas , Laboratórios , Espectrometria de Massas
8.
Sci Total Environ ; 787: 147604, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33992945

RESUMO

The in-utero environmental exposure to fine particulate matter (PM2.5) might lead to adverse birth outcomes, such as low birth weight (LBW) and preterm birth (PTB), thereby increasing susceptibility to diseases in later life. However, no studies have examined the underlying mechanism through cross-omics of lipidome and adipokines profiling, as well as the possible effect modification by maternal hyperlipidemia. In total, 203 mother-newborn pairs were recruited in the birth cohort study ongoing since February 2017 in Beijing, China. Individual-level of PM2.5 exposure was estimated using a satellite data based random forest model. Cord blood lipidome and adipokines were assessed through the lipidomic approaches and antibody-based array. Multivariable logistic/linear regression models and moderation analysis were employed in this study. We observed a significantly increased risk of PTB associated with PM2.5 exposure during the second trimester, especially in pregnant women with pre-existing hyperlipidemia. 9 lipid classes and 21 adipokines were associated with PM2.5 exposure independently or significantly influenced by the interaction of maternal PM2.5 exposure and hyperlipidemia. In addition, 4 adipokines (ANGPTL4, IGFBP-2, IL-12p40, and TNF-RII) and 3 lipid classes [phosphatidylcholines (PCs), phosphatidylinositols (PIs), and triglycerides (TGs)] were related to the increased risk of PTB, indicating that inflammation, IGF/IGFBP axis, and lipolysis induced lipid homeostasis disorder of PCs, TGs, and PIs might be the possible mediators for the PM2.5-induced adverse birth outcomes. Our results substantiated the need for reducing exposure in susceptible populations.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Hiperlipidemias , Nascimento Prematuro , Adipocinas , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Pequim/epidemiologia , China , Estudos de Coortes , Feminino , Humanos , Hiperlipidemias/epidemiologia , Recém-Nascido , Lipidômica , Exposição Materna/efeitos adversos , Material Particulado/efeitos adversos , Material Particulado/análise , Gravidez , Gestantes , Nascimento Prematuro/epidemiologia
9.
J Gen Virol ; 102(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33956593

RESUMO

Host cell lipids play a pivotal role in the pathogenesis of respiratory virus infection. However, a direct comparison of the lipidomic profile of influenza virus and rhinovirus infections is lacking. In this study, we first compared the lipid profile of influenza virus and rhinovirus infection in a bronchial epithelial cell line. Most lipid features were downregulated for both influenza virus and rhinovirus, especially for the sphingomyelin features. Pathway analysis showed that sphingolipid metabolism was the most perturbed pathway. Functional study showed that bacterial sphingomyelinase suppressed influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, but promoted rhinovirus replication. These findings suggest that sphingomyelin pathway can be a potential target for antiviral therapy, but should be carefully evaluated as it has opposite effects on different respiratory viruses. Furthermore, the differential effect of sphingomyelinase on rhinovirus and influenza virus may explain the interference between rhinovirus and influenza virus infection.


Assuntos
Orthomyxoviridae/efeitos dos fármacos , Rhinovirus/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Esfingomielinas/farmacologia , Animais , Broncopatias/virologia , COVID-19/tratamento farmacológico , Linhagem Celular , Cães , Células Epiteliais/virologia , Humanos , Influenza Humana , Lipidômica , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Esfingomielina Fosfodiesterase , Replicação Viral/efeitos dos fármacos
10.
Adv Exp Med Biol ; 1311: 39-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014533

RESUMO

The study of cancer cell metabolism has traditionally focused on glycolysis and glutaminolysis. However, lipidomic technologies have matured considerably over the last decade and broadened our understanding of how lipid metabolism is relevant to cancer biology [1-3]. Studies now suggest that the reprogramming of cellular lipid metabolism contributes directly to malignant transformation and progression [4, 5]. For example, de novo lipid synthesis can supply proliferating tumor cells with phospholipid components that comprise the plasma and organelle membranes of new daughter cells [6, 7]. Moreover, the upregulation of mitochondrial ß-oxidation can support tumor cell energetics and redox homeostasis [8], while lipid-derived messengers can regulate major signaling pathways or coordinate immunosuppressive mechanisms [9-11]. Lipid metabolism has, therefore, become implicated in a variety of oncogenic processes, including metastatic colonization, drug resistance, and cell differentiation [10, 12-16]. However, whether we can safely and effectively modulate the underlying mechanisms of lipid metabolism for cancer therapy is still an open question.


Assuntos
Metabolismo dos Lipídeos , Neoplasias , Transformação Celular Neoplásica , Glicólise , Humanos , Lipidômica
11.
Anal Chem ; 93(16): 6311-6322, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33856206

RESUMO

Lipids and metabolites are of interest in many clinical and research settings because it is the metabolome that is increasingly recognized as a more dynamic and sensitive molecular measure of phenotype. The enormous diversity of lipid structures and the importance of biological structure-function relationships in a wide variety of applications makes accurate identification a challenging yet crucial area of research in the lipid community. Indeed, subtle differences in the chemical structures of lipids can have important implications in cellular metabolism and many disease pathologies. The speed, sensitivity, and molecular specificity afforded by modern mass spectrometry has led to its widespread adoption in the field of lipidomics on many different instrument platforms and experimental workflows. However, unambiguous and complete structural identification of lipids by mass spectrometry remains challenging. Increasingly sophisticated tandem mass spectrometry (MS/MS) approaches are now being developed and seamlessly integrated into lipidomics workflows to meet this challenge. These approaches generally either (i) alter the type of ion that is interrogated or (ii) alter the dissociation method in order to improve the structural information obtained from the MS/MS experiment. In this Perspective, we highlight recent advances in both ion type alteration and ion dissociation methods for lipid identification by mass spectrometry. This discussion is aimed to engage investigators involved in fundamental ion chemistry and technology developments as well as practitioners of lipidomics and its many applications. The rapid rate of technology development in recent years has accelerated and strengthened the ties between these two research communities. We identify the common characteristics and practical figures of merit of these emerging approaches and discuss ways these may catalyze future directions of lipid structural elucidation research.


Assuntos
Lipidômica , Lipídeos , Espectrometria de Massas em Tandem , Metabolismo dos Lipídeos
12.
Int J Mol Sci ; 22(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805070

RESUMO

Lipedema is an adipose tissue disorder characterized by the disproportionate increase of subcutaneous fat tissue in the lower and/or upper extremities. The underlying pathomechanism remains unclear and no molecular biomarkers to distinguish the disease exist, leading to a large number of undiagnosed and misdiagnosed patients. To unravel the distinct molecular characteristic of lipedema we performed lipidomic analysis of the adipose tissue and serum of lipedema versus anatomically- and body mass index (BMI)-matched control patients. Both tissue groups showed no significant changes regarding lipid composition. As hyperplastic adipose tissue represents low-grade inflammation, the potential systemic effects on circulating cytokines were evaluated in lipedema and control patients using the Multiplex immunoassay system. Interestingly, increased systemic levels of interleukin 11 (p = 0.03), interleukin 28A (p = 0.04) and interleukin 29 (p = 0.04) were observed. As cytokines can influence metabolic activity, the metabolic phenotype of the stromal vascular fraction was examined, revealing significantly increased mitochondrial respiration in lipedema. In conclusion, despite sharing a comparable lipid profile with healthy adipose tissue, lipedema is characterized by a distinct systemic cytokine profile and metabolic activity of the stromal vascular fraction.


Assuntos
Tecido Adiposo/metabolismo , Citocinas/metabolismo , Lipedema/metabolismo , Lipídeos/química , Células Estromais/metabolismo , Adulto , Biomarcadores/metabolismo , Biópsia , Índice de Massa Corporal , Feminino , Humanos , Imunoensaio , Inflamação , Metabolismo dos Lipídeos , Lipidômica , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Consumo de Oxigênio , Fenótipo
13.
ACS Chem Neurosci ; 12(8): 1363-1375, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33793210

RESUMO

Traumatic brain injury (TBI) is a complex disease process that may contribute to temporary or permanent disability. Tracking spatial changes of lipids and metabolites in the brain helps unveil the underlying mechanisms of the disease procession and therapeutic response. Here, the liquid microjunction surface sampling technique was used for mass spectrometry imaging of both lipids and metabolites in rat models of controlled cortical impact with and without XueFu ZhuYu decoction treatment, and the work was focused on the diffuse changes outside the injured area at chronic phase (14 days after injury). Quantitative information was provided for phosphotidylcholines and cerebrosides by adding internal standards in the sampling solvent. With principal component analysis for the imaging data, the midbrain was found to be the region with the largest diffuse changes following TBI outside the injured area. In detail, several phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids, and diacylglycerols were found to be significantly up-regulated particularly in midbrain and thalamus after TBI and XFZY treatment. It is associated with the reported "self-repair" mechanisms at the chronic phase of TBI activated by neuroinflammation. Several glycosphingolipids were found to be increased in most of brain regions after TBI, which was inferred to be associated with neuroinflammation and oxidative stress triggered by TBI. Moreover, different classes of small matabolites were significantly changed after TBI, including fatty acids, amino acids, and purines. All these compounds were involved in 10 metabolic pathway networks, and 6 target proteins of XFZY were found related to the impacted pathways. These results shed light on the molecular mechanisms of TBI pathologic processes and therapeutic response.


Assuntos
Lesões Encefálicas Traumáticas , Metaboloma , Animais , Encéfalo/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lipidômica , Espectrometria de Massas , Ratos
14.
Adv Exp Med Biol ; 1280: 39-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791973

RESUMO

Shotgun lipidomics is an analytical approach for large-scale and systematic analysis of the composition, structure, and quantity of cellular lipids directly from lipid extracts of biological samples by mass spectrometry. This approach possesses advantages of high throughput and quantitative accuracy, especially in absolute quantification. As cancer research deepens at the level of quantitative biology and metabolomics, the demand for lipidomics approaches such as shotgun lipidomics is becoming greater. In this chapter, the principles, approaches, and some applications of shotgun lipidomics for cancer research are overviewed.


Assuntos
Lipidômica , Neoplasias , Lipídeos , Espectrometria de Massas , Metabolômica , Pesquisa
15.
Adv Exp Med Biol ; 1280: 173-187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791982

RESUMO

Lipidomics refers to the large-scale study of pathways and networks of cellular lipids in biological systems. A lipidomic analysis often involves the identification and quantification of the thousands of cellular lipid molecular species within a complex biological sample and therefore requires a well optimized method for lipid profiling. In this chapter, the methods for lipidomic analysis, including sample collection and preparation, lipid derivatization and separation, mass spectrometric identification of lipids, data processing and interpretation, and quality control, are overviewed.


Assuntos
Lipidômica , Lipídeos , Espectrometria de Massas , Controle de Qualidade
16.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806352

RESUMO

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. cAMP stimulation also increased the movement of cholesterol from the PM compared to untreated cells, which was partially inhibited when ATPase family AAA-domain containing protein 3 A (ATAD3A), which functions in ER and mitochondria interactions, was knocked down. Mitochondria, ER, cytoplasm, PM, PM-associated membranes (PAMs), and mitochondria-associated membranes (MAMs) were isolated from control and hormone-stimulated cells. Lipidomic analyses revealed that each isolated compartment had a unique lipid composition, and the induction of steroidogenesis caused the significant remodeling of its lipidome. cAMP-induced changes in lipid composition included an increase in phosphatidylserine and cardiolipin levels in PAM and PM compartments, respectively; an increase in phosphatidylinositol in the ER, mitochondria, and MAMs; and a reorganization of phosphatidic acid, cholesterol ester, ceramide, and phosphatidylethanolamine. Abundant lipids, such as phosphatidylcholine, were not affected by hormone treatment. Our data suggested that PM-ER-mitochondria tethering may be involved in lipid trafficking between organelles and indicated that hormone-induced acute steroid production involves extensive organelle remodeling.


Assuntos
Tumor de Células de Leydig/metabolismo , Lipídeos de Membrana/metabolismo , Esteroides/biossíntese , Neoplasias Testiculares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/antagonistas & inibidores , ATPases Associadas a Diversas Atividades Celulares/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Animais , Bucladesina/farmacologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Colesterol/metabolismo , AMP Cíclico/farmacologia , Retículo Endoplasmático/metabolismo , Técnicas de Silenciamento de Genes , Tumor de Células de Leydig/ultraestrutura , Lipidômica , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Modelos Biológicos , Neoplasias Testiculares/ultraestrutura
17.
Signal Transduct Target Ther ; 6(1): 155, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859163

RESUMO

Disease progression prediction and therapeutic drug target discovery for Coronavirus disease 2019 (COVID-19) are particularly important, as there is still no effective strategy for severe COVID-19 patient treatment. Herein, we performed multi-platform omics analysis of serial plasma and urine samples collected from patients during the course of COVID-19. Integrative analyses of these omics data revealed several potential therapeutic targets, such as ANXA1 and CLEC3B. Molecular changes in plasma indicated dysregulation of macrophage and suppression of T cell functions in severe patients compared to those in non-severe patients. Further, we chose 25 important molecular signatures as potential biomarkers for the prediction of disease severity. The prediction power was validated using corresponding urine samples and plasma samples from new COVID-19 patient cohort, with AUC reached to 0.904 and 0.988, respectively. In conclusion, our omics data proposed not only potential therapeutic targets, but also biomarkers for understanding the pathogenesis of severe COVID-19.


Assuntos
COVID-19/sangue , COVID-19/tratamento farmacológico , Descoberta de Drogas , Lipidômica , Proteômica , SARS-CoV-2/metabolismo , Biomarcadores/sangue , Feminino , Humanos , Masculino
18.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801983

RESUMO

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.


Assuntos
Ácidos Graxos/metabolismo , Lipidômica/métodos , Lipídeos/análise , Traumatismo por Reperfusão/terapia , Tecido Adiposo/metabolismo , Animais , Carnitina/metabolismo , Humanos , Lipídeos/química , Mitocôndrias/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/diagnóstico , Traumatismo por Reperfusão/metabolismo
19.
Talanta ; 229: 122262, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33838772

RESUMO

Measuring physiochemically diverse molecules (including lipids) which vary significantly in their concentrations poses a great analytical challenge. In untargeted lipidomics studies, reversed phase chromatography coupled with data-dependent MS/MS acquisition (DDA) is frequently applied. The optimal assay should deliver a high number of detected compounds with associated fragmentation data. In this work, we introduce novel 30 and 50 min UHPLC assays utilising lipid separation on a C30 stationary phase with a modified DDA strategy using smaller precursor m/z ranges scheduled for different lipid classes across the retention time range (defined as scheduled MS/MS). To evaluate the efficiency of the novel assays, mammalian tissue extracts (lamb liver, kidney and heart) were analysed and data were compared to a 15 min reversed phase C18 assay with multiple traditional DDA injections. The 30 min C30 assay detected double the number of detected compounds compared to the 15 min C18 assay. Applying the scheduled MS/MS DDA strategy with a single injection, a similar number of annotated lipids were reported compared to the traditional DDA strategy applied with five replicate injections on a C18 column. A longer 50 min C30 chromatographic assay did not result in an expected improvement in the chromatographic separation of overlapping isomer peaks compared to the 30 min method but did result in loss of accuracy of peak picking algorithms. We recommend the 30 min C30 assay with scheduled MS/MS acquisition as an efficient tool to analyse complex biological matrices and to annotate lipid species based on MS/MS data.


Assuntos
Lipídeos , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Lipidômica , Ovinos
20.
Int J Mol Sci ; 22(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924531

RESUMO

Bacteria form multicellular and resistant structures named biofilms. Biofilm formation starts with the attachment phase, and the molecular actors involved in this phase, except adhesins, are poorly characterized. There is growing evidence that phospholipids are more than simple structural bricks. They are involved in bacterial adaptive physiology, but little is known about their role in biofilm formation. Here, we report a mass spectrometry analysis of the phospholipid (PL) profile of several strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. The aim of our study was to evaluate a possible link between the PL profile of a strain and its attachment phenotype. Our results showed that PL profile is strongly strain-dependent. The PL profile of P. aeruginosa PAO1, a collection strain, was different from those of 10 clinical isolates characterized either by a very low or a very high attachment capacity. We observed also that the clinical strain's PL profiles varied even more importantly between isolates. By comparing groups of strains having similar attachment capacities, we identified one PL, PE 18:1-18:1, as a potential molecular actor involved in attachment, the first step in biofilm formation. This PL represents a possible target in the fight against biofilms.


Assuntos
Aderência Bacteriana , Fosfolipídeos/metabolismo , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Humanos , Lipidômica , Análise de Componente Principal , Reprodutibilidade dos Testes
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