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1.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800808

RESUMO

Plants are subject to different types of stress, which consequently affect their growth and development. They have developed mechanisms for recognizing and processing an extracellular signal. Second messengers are transient molecules that modulate the physiological responses in plant cells under stress conditions. In this sense, it has been shown in various plant models that membrane lipids are substrates for the generation of second lipid messengers such as phosphoinositide, phosphatidic acid, sphingolipids, and lysophospholipids. In recent years, research on lipid second messengers has been moving toward using genetic and molecular approaches to reveal the molecular setting in which these molecules act in response to osmotic stress. In this sense, these studies have established that second messengers can transiently recruit target proteins to the membrane and, therefore, affect protein conformation, activity, and gene expression. This review summarizes recent advances in responses related to the link between lipid second messengers and osmotic stress in plant cells.


Assuntos
Lipídeos/fisiologia , Pressão Osmótica/fisiologia , Plantas/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Cálcio/metabolismo , Glicolipídeos/fisiologia , Modelos Biológicos , Fosfolipídeos/fisiologia , Proteínas de Plantas/metabolismo , Estresse Salino/fisiologia
2.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540695

RESUMO

Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario. Indeed, MSCs are a heterogenous population of multipotent cells that have attracted much attention for their potential in regulating inflammation, immunomodulatory capabilities, and reparative roles. The lipidomics of the inflammatory disease osteoarthritis (OA) and the influence of MSCs-derived lipids have also been addressed.


Assuntos
Inflamação/metabolismo , Lipídeos/fisiologia , Células-Tronco Mesenquimais/metabolismo , Imunidade Adaptativa , Animais , Diferenciação Celular , Eicosanoides/fisiologia , Endocanabinoides/fisiologia , Vesículas Extracelulares , Ácidos Graxos Insaturados/farmacologia , Humanos , Imunidade Inata , Inflamação/imunologia , Lipídeos/classificação , Lisofosfolipídeos/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoartrite/metabolismo , Osteoartrite/terapia
3.
Nat Chem Biol ; 17(4): 465-476, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542532

RESUMO

Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca2+-independent phospholipase A2ß (iPLA2ß, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA2ß averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinson's disease (PD)-associated mutation (fPDR747W) and found selectively decreased 15-HpETE-PE-hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-Cas9-engineered Pnpla9R748W/R748W mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and α-synuclein-mutant SncaA53T mice, with decreased iPLA2ß expression and a PD-relevant phenotype. Thus, iPLA2ß is a new ferroptosis regulator, and its mutations may be implicated in PD pathogenesis.


Assuntos
Ferroptose/fisiologia , Fosfolipases A2 do Grupo VI/metabolismo , Animais , Araquidonato 15-Lipoxigenase/metabolismo , Modelos Animais de Doenças , Feminino , Fosfolipases A2 do Grupo VI/fisiologia , Humanos , Ferro/metabolismo , Leucotrienos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Peróxidos Lipídicos/metabolismo , Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Doença de Parkinson/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos Lew
4.
PLoS One ; 15(9): e0239547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970728

RESUMO

Obesity is a common disease over the world and is tightly associated with diabetes mellitus, cardiovascular and cancer disease. Although our previous study showed that the synthetic vanadium-protein (V-P) complex had a better effect on antioxidant and antidiabetic, the relative molecular mechanisms are still entirely unknown. Hence, we investigated the effect of the synthetic V-P complex on adipocyte differentiation (adipogenesis) using human preadipocytes to clarify its molecular mechanisms of action. The primary human preadipocytes were cultured with and without V-P complex during adipocyte differentiation. The cell proliferation, lipid accumulation, and the protein expression of transcription factors and related enzymes were determined for the differentiated human preadipocytes. In this study, the 20 µg/mL of V-P complex reduced the lipid and triglyceride (TG) content by 74.47 and 57.39% (p < 0.05), respectively, and down-regulated the protein expressions of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthase (FAS). Additionally, the V-P complex significantly up-regulated the protein levels of total ß-catenin (t-ß-catenin), nuclear ß-catenin (n-ß-catenin), phosphorylated adenosine monophosphate-activated protein kinase alpha (p-AMPKα) and liver kinase B1 (p-LKB1). These showed that the inhibitory effect of V-P complex on human adipogenesis was mediated by activating Wnt/ß-catenin and LKB1/AMPK-dependent signaling pathway. Therefore, the synthetic V-P complex could be considered as a candidate for prevention and treatment of obesity.


Assuntos
Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Vanádio/metabolismo , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Diferenciação Celular/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Camundongos , Obesidade/metabolismo , PPAR gama/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Triglicerídeos/metabolismo , beta Catenina/metabolismo
5.
Cell ; 181(2): 293-305.e11, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32142653

RESUMO

Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.


Assuntos
Tosse/fisiopatologia , Glicolipídeos/metabolismo , Nociceptores/fisiologia , Fatores de Virulência/metabolismo , Adulto , Animais , Linhagem Celular , Tosse/etiologia , Tosse/microbiologia , Feminino , Glicolipídeos/fisiologia , Cobaias , Interações Hospedeiro-Patógeno , Humanos , Lipídeos/fisiologia , Pulmão/microbiologia , Macrófagos/microbiologia , Masculino , Camundongos , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidade , Cultura Primária de Células , Tuberculose/microbiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/fisiopatologia , Fatores de Virulência/fisiologia
6.
Int J Mol Sci ; 21(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178449

RESUMO

Both glucose and free fatty acids (FFAs) are used as fuel sources for energy production in a living organism. Compelling evidence supports a role for excess fatty acids synthesized in intramuscular space or dietary intermediates in the regulation of skeletal muscle function. Excess FFA and lipid droplets leads to intramuscular accumulation of lipid intermediates. The resulting downregulation of the insulin signaling cascade prevents the translocation of glucose transporter to the plasma membrane and glucose uptake into skeletal muscle, leading to metabolic disorders such as type 2 diabetes. The mechanisms underlining metabolic dysfunction in skeletal muscle include accumulation of intracellular lipid derivatives from elevated plasma FFAs. This paper provides a review of the molecular mechanisms underlying insulin-related signaling pathways after excess accumulation of lipids.


Assuntos
Resistência à Insulina/fisiologia , Insulina/metabolismo , Lipídeos/fisiologia , Músculo Esquelético/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Transdução de Sinais/fisiologia
7.
Curr Opin Cell Biol ; 63: 162-173, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106003

RESUMO

The lipids that make up biological membranes tend to be the forgotten molecules of cell biology. The paucity of data on these important entities likely reflects the difficulties of studying and understanding their biological roles, rather than revealing a lack of importance. Indeed, the lipid composition of biological membranes has a profound impact on a diverse array of cellular processes. The focus of this review is on the effects of different lipid classes on the function of mitochondria, particularly bioenergetics, in health and disease.


Assuntos
Membrana Celular/química , Membrana Celular/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Mitocôndrias/fisiologia , Animais , Fenômenos Fisiológicos Celulares , Humanos , Lipídeos/química , Mitocôndrias/metabolismo
8.
Mol Biol Cell ; 31(3): 143-148, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31999511

RESUMO

While the organization of inanimate systems such as gases or liquids is predominantly thermodynamically driven-a mixture of two gases will tend to mix until they reach equilibrium-biological systems frequently exhibit organization that is far from a well-mixed equilibrium. The anisotropies displayed by cells are evident in some of the dynamic processes that constitute life including cell development, movement, and division. These anisotropies operate at different length-scales, from the meso- to the nanoscale, and are proposed to reflect self-organization, a characteristic of living systems that is becoming accessible to reconstitution from purified components, and thus a more thorough understanding. Here, some examples of self-organization underlying cellular anisotropies at the cellular level are reviewed, with an emphasis on Rho-family GTPases operating at the plasma membrane. Given the technical challenges of studying these dynamic proteins, some of the successful approaches that are being employed to study their self-organization will also be considered.


Assuntos
Anisotropia , Fenômenos Fisiológicos Celulares/fisiologia , Células/metabolismo , Actinas/metabolismo , Animais , Membrana Celular/metabolismo , Membrana Celular/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Humanos , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Termodinâmica , Proteínas rho de Ligação ao GTP/metabolismo
9.
Genes Cells ; 25(1): 65-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31721365

RESUMO

Atg2 is one of the essential factors for autophagy. Recent advance of structural and biochemical study on yeast Atg2 proposed that Atg2 tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum and mediates direct lipid transfer (LT) from ER to IM for IM expansion. In mammals, two Atg2 orthologs, ATG2A and ATG2B, participate in autophagic process. Here we showed that human ATG2B possesses the membrane tethering (MT) and LT activity that was promoted by negatively charged membranes and an Atg18 ortholog WIPI4. By contrast, negatively charged membranes reduced the yeast Atg2 activities in the absence of Atg18. These results suggest that the MT/LT activity of Atg2 is evolutionally conserved although their regulation differs among species.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/fisiologia , Transporte Biológico , Proteínas de Transporte/fisiologia , Retículo Endoplasmático/metabolismo , Humanos , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Proteínas de Ligação a Fosfato/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Transporte Vesicular/fisiologia
10.
Mol Biol Cell ; 31(1): 7-17, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746669

RESUMO

The unfolded protein response (UPR) senses defects in the endoplasmic reticulum (ER) and orchestrates a complex program of adaptive cellular remodeling. Increasing evidence suggests an important relationship between lipid homeostasis and the UPR. Defects in the ER membrane induce the UPR, and the UPR in turn controls the expression of some lipid metabolic genes. Among lipid species, the very-long-chain fatty acids (VLCFAs) are relatively rare and poorly understood. Here, we show that loss of the VLCFA-coenzyme A synthetase Fat1, which is essential for VLCFA utilization, results in ER stress with compensatory UPR induction. Comprehensive lipidomic analyses revealed a dramatic increase in membrane saturation in the fat1Δ mutant, likely accounting for UPR induction. In principle, this increased membrane saturation could reflect adaptive membrane remodeling or an adverse effect of VLCFA dysfunction. We provide evidence supporting the latter, as the fat1Δ mutant showed defects in the function of Ole1, the sole fatty acyl desaturase in yeast. These results indicate that VLCFAs play essential roles in protein quality control and membrane homeostasis and suggest an unexpected requirement for VLCFAs in Ole1 function.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Coenzima A Ligases/metabolismo , Retículo Endoplasmático/fisiologia , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Homeostase , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Membranas/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Resposta a Proteínas não Dobradas/genética
11.
J Dermatolog Treat ; 31(7): 716-722, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30998081

RESUMO

Dry skin is a common condition that is attributed to a lack of water in the stratum corneum. With the availability of new technologies, light has been shed on the pathophysiology of dry skin at the molecular level. With the aim to discuss implications of this latest research for the optimal formulation of emollients designed to treat dry skin, five specialists met in November 2017. Research on three topics thereby provided particularly detailed new insights on how to manage dry skin: research on the lipid composition and organization of the stratum corneum, research on natural moisturizing factors, and research on the peripheral nervous system. There was consensus that latest research expands the rationale to include physiological lipids in an emollient used for dry skin, as they were found to be essential for an adequate composition and organization in the stratum corneum but are reduced in dry skin. Latest findings also confirmed the incorporation of carefully selected humectants into a topical emollient for dry skin, given the reduced activity of enzymes involved in the synthesis of moisturizing factors when skin is dry. Overall, the group of specialists concluded that the previous concept of the five components for an ideal emollient for dry skin is well in accordance with latest research.


Assuntos
Emolientes/administração & dosagem , Fenômenos Fisiológicos da Pele , Administração Cutânea , Epiderme/fisiologia , Humanos , Lipídeos/fisiologia , Higiene da Pele , Dermatopatias/genética , Água/fisiologia
12.
Biochim Biophys Acta Gen Subj ; 1864(3): 129487, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31734461

RESUMO

BACKGROUND: Skeletal muscle cells continuously generate reactive oxygen species (ROS). Excessive ROS can affect lipids resulting in lipid peroxidation (LPO). Here we investigated the effects of myotube intracellular calcium-induced signaling eliciting contractions on the LPO induction and the impact of LPO-product 4-hydroxynonenal (4-HNE) on physiology/pathology of myotubes using C2C12 myoblasts. METHODS: C2C12 myoblasts were differentiated into myotubes, stimulated with caffeine and analyzed for the induction of LPO and formation of 4-HNE protein adducts. Further effects of 4-HNE on mitochondrial bioenergetics, NADH level, mitochondrial density and expression of mitochondrial metabolism genes were determined. RESULTS: Short and long-term caffeine stimulation of myotubes promoted superoxide production, LPO and formation of 4-HNE protein adducts. Furthermore, low 4-HNE concentrations had no effect on myotube viability and cellular redox homeostasis, while concentrations from 10 µM and above reduced myotube viability and significantly disrupted homeostasis. A time and dose-dependent 4-HNE effect on superoxide production and mitochondrial NADH-autofluorescence was observed. Finally, 4-HNE had strong impact on maximal respiration, spare respiratory capacity, ATP production, coupling efficiency of mitochondria and mitochondrial density. CONCLUSION: Data presented in this work make evident for the first time that pathological 4-HNE levels elicit damaging effects on skeletal muscle cells while acute exposure to physiological 4-HNE induces transient adaptation. GENERAL SIGNIFICANCE: This work suggests an important role of 4-HNE on the regulation of myotube's mitochondrial metabolism and cellular energy production. It further signifies the importance of skeletal muscle cells hormesis in response to acute stress in order to maintain essential biological functions.


Assuntos
Cálcio/metabolismo , Peroxidação de Lipídeos/fisiologia , Mitocôndrias/metabolismo , Aldeídos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cafeína/farmacologia , Cálcio/fisiologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Metabolismo Energético , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Mioblastos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxidos/metabolismo
13.
J Nat Med ; 74(1): 252-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31267355

RESUMO

The lycopene content of tomatoes is important because of its effects on vital physiological functions such as improvement of glucose tolerance and non-alcoholic fatty liver disease. To investigate the influence of the lycopene content of tomatoes on glucose tolerance and hepatic lipid content, homogenates of lycopene-rich (LR) or lycopene-free negative control (NC) tomato varieties were administrated to normal rats for 4 weeks. At the end of the experiment, an oral glucose tolerance test (OGTT) was performed. Rats were fed once and then dissected. According to the OGTT results, plasma glucose levels in the LR group were 10% and 9% lower at 15 min and 30 min, respectively, than those in the NC group, whereas plasma insulin levels did not differ between the groups at either time point. Upon dissection, plasma leptin levels in the LR group were higher than those in the NC group, while plasma adiponectin levels did not differ between groups. With the exception of retinol palmitate, no carotenoids were detected in the liver by HPLC analysis. Hepatic retinol palmitate levels and hepatic triacyl glyceride levels did not differ between the groups. We concluded that in normal rats, a lycopene-rich tomato variety improved glucose tolerance via an increase in plasma leptin levels that enhanced insulin sensitivity but did not affect carotenoid accumulation or lipid metabolism.


Assuntos
Glicemia/efeitos dos fármacos , Insulina/sangue , Leptina/sangue , Licopeno/análise , Lycopersicon esculentum/química , Adiponectina/sangue , Animais , Carotenoides/análise , Cromatografia Líquida de Alta Pressão , Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Homeostase , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Masculino , Ratos
14.
Biochim Biophys Acta Biomembr ; 1862(3): 183160, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874147

RESUMO

Membrane curvature sensing via helical protein domains, such as those identified in Amphiphysin and ArfGAP1, have been linked to a diverse range of cellular processes. However, these regions can vary significantly between different protein families and thus remain challenging to identify from sequence alone. Greater insight into the protein-lipid interactions that drive this behavior could lead to production of therapeutics that specifically target highly curved membranes. Here we demonstrate the curvature-dependence of membrane binding for an amphipathic helix (APH) in a plant reticulon, namely RTNLB13 from A. thaliana. We utilize solution-state nuclear magnetic resonance spectroscopy to establish the exact location of the APH and map the residues involved in protein-membrane interactions at atomic resolution. We find that the hydrophobic residues making up the membrane binding site are conserved throughout all A. thaliana reticulons. Our results also provide mechanistic insight that leads us to propose that membrane binding by this APH may act as a feedback element, only forming when ER tubules reach a critical size and adding stabilization to these structures without disrupting the bilayer. A shallow hydrophobic binding interface appears to be a feature shared more broadly across helical curvature sensors and would automatically restrict the penetration depth of these structures into the membrane. We also suggest this APH is highly tuned to the composition of the membrane in which it resides, and that this property may be universal in curvature sensors thus rationalizing the variety of mechanisms reported for these functional elements.


Assuntos
Retículo Endoplasmático/metabolismo , Lipídeos/fisiologia , Proteínas de Membrana/metabolismo , Sequência de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Fenômenos Biofísicos , Membrana Celular/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/análise , Lipossomos/química , Domínios Proteicos , Dobramento de Proteína
15.
Adv Exp Med Biol ; 1185: 289-293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884626

RESUMO

The retinal pigment epithelium (RPE) is a monolayer of pigmented cells whose function is essential for the integrity of the retina and for visual function. Retinal diseases that eventually end in vision loss and blindness involve inflammation, oxidative stress (OS), and alterations in the RPE-photoreceptor cellular partnership. This chapter summarizes the role of lipid signaling pathways and lipidic molecules in RPE cells exposed to inflammatory and OS conditions. The modulation of these pathways in the RPE, through either enzyme inhibitors or receptor stimulation or blockage, could open new therapeutic strategies for retinal degenerative diseases.


Assuntos
Lipídeos/fisiologia , Estresse Oxidativo , Degeneração Retiniana/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Transdução de Sinais , Humanos , Epitélio Pigmentado da Retina/citologia
16.
Oxid Med Cell Longev ; 2019: 4393460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885792

RESUMO

Despite the proven role of oxidative stress in numerous systemic diseases and in the process of aging, little is still known about the salivary redox balance of healthy children, adults, and the elderly. Our study was the first to assess the antioxidant barrier, redox status, and oxidative damage in nonstimulated (NWS) and stimulated (SWS) saliva as well as blood samples of healthy individuals at different ages. We divided 90 generally healthy people into three equally numbered groups based on age: 2-14 (children and adolescents), 25-45 (adults), and 65-85 (elderly people). Antioxidant enzymes (salivary peroxidase (Px), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase-1 (SOD)), nonenzymatic antioxidants (reduced glutathione (GSH) and uric acid (UA)), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and malondialdehyde (MDA)) were evaluated in NWS and SWS as well as in erythrocyte/plasma samples. We demonstrated that salivary and blood antioxidant defense is most effective in people aged 25-45. In the elderly, we observed a progressive decrease in the efficiency of central antioxidant systems (↓GPx, ↓SOD, ↓GSH, and ↓TAC in erythrocytes and plasma vs. adults) as well as in NWS (↓Px, ↓UA, and ↓TAC vs. adults) and SWS (↓TAC vs. adults). Both local and systemic antioxidant systems were less efficient in children and adolescents than in the group of middle-aged people, which indicates age-related immaturity of antioxidant mechanisms. Oxidative damage to proteins (↑AGE, ↑AOPP) and lipids (↑MDA) was significantly higher in saliva and plasma of elderly people in comparison with adults and children/adolescents. Of all the evaluated biomarkers, only salivary oxidative damage products generally reflected their content in blood plasma. The level of salivary redox biomarkers did not vary based on gender.


Assuntos
Antioxidantes/metabolismo , Lipídeos/fisiologia , Proteínas/metabolismo , Saliva/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo , Saliva/citologia , Adulto Jovem
17.
Oxid Med Cell Longev ; 2019: 4521786, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885793

RESUMO

Lipid metabolic disorders due to poor eating habits are on the rise in both developed and developing countries, with a negative impact of the "Western diet" on sperm count and quality. Dietary lipid imbalance can involve cholesterol, fatty acids, or both, under different pathophysiological conditions grouped under the term dyslipidemia. The general feature of dyslipidemia is the development of systemic oxidative stress, a well-known deleterious factor for the quality of male gametes and associated with infertility. Sperm are particularly rich in polyunsaturated fatty acids (PUFA), an important characteristic associated with normal sperm physiology and reproductive outcomes, but also targets of choice for oxidative thrust. This review focuses on the effects of dietary cholesterol or different fatty acid overload on sperm composition and function in both animals and humans. The links between oxidative stress induced by dyslipidemia and sperm dysfunction are then discussed, including possible preventive or therapeutic strategies to preserve gamete quality, longevity when stored in cryobanking, and male fertility.


Assuntos
Colesterol na Dieta/metabolismo , Fertilidade/fisiologia , Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Animais , Modelos Animais de Doenças , Humanos , Masculino
18.
Cells ; 8(11)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683987

RESUMO

Ectopic lipid accumulation in muscle is important not only for obesity and myopathy treatment, but also for meat quality improvement in farm animals. However, the molecular mechanisms involved in lipid metabolism in muscle satellite cells are still elusive. In this study, SB216763 reduced GSK3ß activation by increasing the level of pGSK3ß (Ser9) and decreasing the level of total GSK3ß protein. GSK3ß inhibition decreased lipid accumulation and downregulated the expression level of lipogenesis-related genes in the adipogenic differentiation of goat muscle satellite cells. Furthermore, SB216763 treatment increased the levels of pAMPKα (T172) and pACC (Ser79). Further, we found that GSK3ß inhibition promoted levels of LC3B-II and reduced the protein levels of p62 to induce the autophagy in muscle satellite cells. Taken together, our results provide new insight into a critical function for GSK3ß: modulating lipid accumulation in goat muscle satellite cells through activating the AMPK pathway.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Metabolismo dos Lipídeos/fisiologia , Células Satélites de Músculo Esquelético/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia/fisiologia , Diferenciação Celular , Linhagem Celular , Cabras/metabolismo , Indóis/farmacologia , Lipídeos/fisiologia , Maleimidas/farmacologia , Músculos/metabolismo , Mioblastos/metabolismo , Fosforilação , Transdução de Sinais
19.
Curr Diab Rep ; 19(12): 144, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754839

RESUMO

PURPOSE OF REVIEW: The goal of this review is to review the role that renal parenchymal lipid accumulation plays in contributing to diabetic kidney disease (DKD), specifically contributing to the mitochondrial dysfunction observed in glomerular renal cells in the context of DKD development and progression. RECENT FINDINGS: Mitochondrial dysfunction has been observed in experimental and clinical DKD. Recently, Ayanga et al. demonstrate that podocyte-specific deletion of a protein involved in mitochondrial dynamics protects from DKD progression. Furthermore, our group has recently shown that ATP-binding cassette A1 (a protein involved in cholesterol and phospholipid efflux) is significantly reduced in clinical and experimental DKD and that genetic or pharmacological induction of ABCA1 is sufficient to protect from DKD. ABCA1 deficiency in podocytes leads to mitochondrial dysfunction observed with alterations of mitochondrial lipids, in particular, cardiolipin (a mitochondrial-specific phospholipid). However, through pharmacological reduction of cardiolipin peroxidation DKD progression is reverted. Lipid metabolism is significantly altered in the diabetic kidney and renders cellular components, such as the podocyte, susceptible to injury leading to worsened DKD progression. Dysfunction of the lipid metabolism pathway can also lead to mitochondrial dysfunction and mitochondrial lipid alteration. Future research aimed at targeting mitochondrial lipids content and function could prove to be beneficial for the treatment of DKD.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Glomérulos Renais/fisiopatologia , Transtornos do Metabolismo dos Lipídeos/fisiopatologia , Metabolismo dos Lipídeos/fisiologia , Mitocôndrias/fisiologia , Receptor Cross-Talk/fisiologia , Nefropatias Diabéticas/etiologia , Humanos , Glomérulos Renais/patologia , Transtornos do Metabolismo dos Lipídeos/etiologia , Lipídeos/fisiologia , Podócitos/fisiologia
20.
Int J Mol Sci ; 20(21)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671745

RESUMO

Liver X receptors (LXRs) are ligand-dependent transcription factors acting as 'cholesterol sensors' to regulate lipid homeostasis in cells. The two isoforms, LXRα (NR1H3) and LXRß (NR1H2), are differentially expressed, with the former expressed predominantly in metabolically active tissues and the latter more ubiquitously. Both are activated by oxidised cholesterol metabolites, endogenously produced oxysterols. LXRs have important roles in lipid metabolism and inflammation, plus a number of newly emerging roles. They are implicated in regulating lipid balance in normal male reproductive function and may provide a link between male infertility and lipid disorders and/or obesity. Studies from Lxr knockout mouse models provide compelling evidence to support this. More recently published data suggest distinct and overlapping roles of the LXR isoforms in the testis and recent evidence of a role for LXRs in human male fertility. This review summarises the current literature and explores the likely link between LXR, lipid metabolism and male fertility as part of a special issue on Liver X receptors in International Journal of Molecular Sciences.


Assuntos
Fertilidade/fisiologia , Infertilidade Masculina/metabolismo , Receptores X do Fígado/metabolismo , Animais , Colesterol/metabolismo , Epididimo/crescimento & desenvolvimento , Epididimo/metabolismo , Regulação da Expressão Gênica , Homeostase , Humanos , Inflamação/metabolismo , Metabolismo dos Lipídeos , Lipídeos/fisiologia , Receptores X do Fígado/química , Receptores X do Fígado/genética , Masculino , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Oxisteróis/metabolismo , Isoformas de Proteínas/metabolismo , Células de Sertoli/metabolismo , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
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