ABSTRACT
Psoriasis is a polygenic, inflammatory and progressive disease, characterized by an abnormal differentiation and hyperproliferation of keratinocytes, associated with impaired immunologic activation and systemic disorders, while psoriatic arthritis is a chronic inflammatory articular disease. Pathophysiology of psoriasis comprises a dysfunction of the immune system cells with an interactive network between cells and cytokines supporting the initiation and perpetuation of disease and leading to inflammation of skin, enthesis and joints. Recent studies have shown an important role of systemic inflammation in the development of atherosclerosis. Corroborating these findings, patients with severe Psoriasis have marked incidence of psoriatic arthritis, cardiovascular diseases, hypertension, dyslipidemia, obesity and diabetes mellitus, showing an increased risk for acute myocardial infarction, which suggests that the condition is not restricted to the skin. Nuclear receptors are ligand-dependent transcription factors, whose activation affects genes that control vital processes. Among them the peroxisome proliferator-activated receptor is responsible for establishing the relationship between lipids, metabolic diseases and innate immunity. In the skin, peroxisome proliferator-activated receptors have an important effect in keratinocyte homeostasis, suggesting a role in diseases such as psoriasis. The peroxisome proliferator-activated receptors agonists represent a relevant source of research in the treatment of skin conditions, however more clinical studies are needed to define the potential response of these drugs in patients with psoriasis and psoriatic arthritis.
A psoríase é uma doença poligênica, inflamatória, progressiva e recorrente, caracterizada por um ciclo evolutivo acelerado dos queratinócitos, associado à ativação imune desordenada e a alterações sistêmicas correlacionadas, sendo a artrite psoriásica o comprometimento articular inflamatório crônico que pode ocorrer em pacientes com a doença cutânea. Na inflamação autoimune, uma rede interativa entre células e citocinas suporta o início e a perpetuação da doença. A fisiopatologia da psoríase e da artrite psoriásica compreende uma disfunção das células do sistema imune e da rede de citocinas, levando à inflamação de pele, enteses e articulações. Estudos recentes têm demonstrado um papel importante da inflamação sistêmica no desenvolvimento da aterosclerose. Corroborando esses achados, pacientes portadores de psoríase grave apresentam marcada incidência de artrite psoriásica, doença cardiovascular, hipertensão arterial sistêmica, dislipidemia, obesidade e diabetes mellitus, evidenciando um risco aumentado para infarto agudo do miocárdio e sugerindo que a doença não se restringe à pele. Os receptores nucleares são fatores de transcrição ligante-dependente cuja ativação afeta genes controladores de processos vitais. Entre eles, destacam-se os receptores ativados pelo proliferador de peroxissoma, responsáveis por estabelecer a relação entre os lipídios, doenças metabólicas e imunidade inata. Na pele, os receptores ativados pelo proliferador de peroxissoma têm ação importante na homeostase dos ceratinócitos, exibindo uma função pró-diferenciação, antiproliferativa e imunomoduladora, sugerindo um papel relevante ...
Subject(s)
Humans , Arthritis, Psoriatic/drug therapy , Peroxisome Proliferator-Activated Receptors/agonists , Psoriasis/drug therapy , Anti-Inflammatory Agents/therapeutic use , Arthritis, Psoriatic/metabolism , Cytokines/metabolism , Immunologic Factors/therapeutic use , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , Peroxisome Proliferator-Activated Receptors/metabolism , Psoriasis/metabolismABSTRACT
Nitro-fatty acids are formed and detected in human plasma, cell membranes, and tissue, modulating metabolic as well as inflammatory signaling pathways. Here we discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, redirecting arachidonic acid metabolism and signaling. We also analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases.
Subject(s)
Humans , Anti-Inflammatory Agents/metabolism , Arachidonic Acid/metabolism , Fatty Acids/biosynthesis , Nitric Oxide/metabolism , Nitro Compounds/metabolism , Signal Transduction/physiology , Anti-Inflammatory Agents/chemistry , Fatty Acids/chemistry , Heme Oxygenase-1/metabolism , NADPH Oxidases/metabolism , /metabolism , NF-kappa B/metabolism , Nitro Compounds/chemistry , Peroxisome Proliferator-Activated Receptors/metabolism , Prostaglandin-Endoperoxide Synthases/metabolismABSTRACT
A obesidade é um dos principais problemas de saúde pública. Indivíduos obesos são mais suscetíveis a desenvolver doenças cardiovasculares e diabetes melito tipo 2. A obesidade resulta do aumento no tamanho e no número de adipócitos. O balanço entre adipogênese e adiposidade determina o grau de obesidade do indivíduo. Adipócitos maduros secretam adipocinas, tais como TNFα, IL-6, leptina e adiponectina, e lipocina, o ácido palmitoleico ω-7. A produção de adipocinas é maior na obesidade, o que contribui para o estabelecimento de resistência periférica à insulina. O conhecimento dos eventos moleculares que regulam a diferenciação dos pré-adipócitos e de células-tronco mesenquimais em adipócitos (adipogênese) é importante para o entendimento da gênese da obesidade. A ativação do fator de transcrição PPARγ é essencial na adipogênese. Certos ácidos graxos são ligantes de PPARγ e podem, assim, controlar a adipogênese. Além disso, alguns ácidos graxos atuam como moléculas sinalizadoras em adipócitos, regulando sua diferenciação ou morte. Dessa forma, a composição lipídica da dieta e os agonistas de PPARγ podem regular o balanço entre adipogênese e morte de adipócitos e, portanto, a obesidade.
Obesity is one of the major Public Health problems. Obese individuals are more susceptible to develop cardiovascular diseases and type 2 diabetes mellitus. The obesity results from the increase in size and number of the adipocytes. The balance between adipogenesis and adiposity determines the degree of obesity. Mature adipocytes secrete adipokines, such as TNFα, IL-6, leptine and adiponectin, and lipokine, the palmitoleic acid ω-7. The production of adipokines is increased in obesity, contributing to the onset of peripheral insulin resistance. The knowledge about the molecular events that regulate the differentiation of pre-adipocytes and mesenchymal stem cells into adipocytes (adipogenesis) is important for the comprehension of the genesis of obesity. Activation of transcription factor PPARγ plays an essential role in the adipogenesis. Certain fatty acids are PPARγ ligands and can control adipogenesis. Moreover, some fatty acids act as signaling molecules regulating their differentiation into adipocytes or death. Accordingly, the lipid composition of the diet and PPARγ agonists can regulate the balance between adipogenesis and death of adipocytes and, therefore, the obesity.
Subject(s)
Animals , Humans , Adipogenesis/physiology , Adipose Tissue/metabolism , Cardiovascular Diseases , Fatty Acids/metabolism , Obesity/metabolism , Peroxisome Proliferator-Activated Receptors/metabolism , Adipogenesis/drug effects , Adipose Tissue/drug effects , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Fatty Acids/therapeutic use , Linoleic Acids, Conjugated/metabolismABSTRACT
In the feto-placental unit, preferential transport of maternal plasma arachidonic acid (20:4n-6) and docosahexaenoic acid (22:5n-3) across the placenta is of critical importance for fetal growth and development. More than 90 per cent of the fat deposition in the fetus occurs in the last 10 weeks of pregnancy. All of the n -3 and n -6 fatty acid structures acquired by the fetus have to cross the placenta and fetal blood are enriched in long chain polyunsaturated fatty acids (LCPUFA) relative to the maternal supply. Fatty acids cross the placental microvillous and basal membranes by simple diffusion and via the action of membrane bound (FAT, FATP and p-FABPpm) and cytoplasmic fatty acid-binding proteins (FABPs). The direction and magnitude of fatty acid flux is mainly dictated by the relative abundance of available binding sites. The existence of a fatty-acid-transport system comprising multiple binding proteins in human placenta may be essential to facilitate the preferential transport of maternal plasma fatty acids in order to meet the requirements of the growing fetus. The critical importance of long-chain fatty acids in cellular homeostasis demands an efficient uptake system for these fatty acids and their metabolism in tissues. In fact, involvement of several nuclear transcription factors (PPARgamma, LXR, RXR, and SREBP-1) is critical in the expression of genes responsible for fatty acids uptake, placental trophoblast differentiation and hCG production. These indicate that these receptors are potential regulators of placental lipid transfer and homeostasis. This review discusses importance of nuclear receptors and fatty acid binding/transport proteins in placental fatty acid uptake, transport and metabolism.
Subject(s)
CCAAT-Enhancer-Binding Proteins/metabolism , Carrier Proteins/metabolism , DNA-Binding Proteins/metabolism , Fatty Acid Transport Proteins , Fatty Acid-Binding Proteins , Female , Fetal Development , Gene Expression , Humans , Membrane Transport Proteins/metabolism , Models, Biological , Peroxisome Proliferator-Activated Receptors/metabolism , Placenta/metabolism , Pregnancy , Receptors, Cytoplasmic and Nuclear/metabolism , Sterol Regulatory Element Binding Protein 1 , Transcription Factors/metabolismABSTRACT
No abstract available.
Subject(s)
Humans , Peroxisome Proliferator-Activated Receptors/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Stomach Neoplasms/metabolismABSTRACT
BACKGROUND/AIMS: Gastric cancer is still the most frequently diagnosed malignancy in Korea. It has been reported that COX-2 and PPAR are involved in multi-step gastric carcinogenesis. The aim of the present study was to examine the expression of COX-2 and PPAR in gastric cancer. METHODS: A total of 75 subjects including 45 patients with gastric cancer and 30 controls were enrolled. All subjects underwent upper gastrointestinal endoscopic examination with tissue collection. mRNA extraction from the tissues and real-time PCR for COX-2, PPAR-delta, and PPAR-gamma were performed. Gastric mucosal concentration of PGE2, which is a final product of COX-2, and 15d-PGJ2, which is a ligand of PPAR-gamma, were measured by the enzyme immunoassay method. RESULTS: COX-2 mRNA expression was significantly higher in both early gastric cancer tissues (EGC, 8.32 +/- 4.84 micro gram/micro L, p<0.005) and advanced gastric cancer tissues (AGC, 8.16 +/- 2.67 micro gram/micro L, p<0.001) than in non-cancerous tissues of controls (3.46 +/- 1.72 micro gram/micro L). There was no significant difference of PPAR-delta and PPAR-gamma mRNA expression between gastric cancer tissues and controls. Mucosal PGE2 concentration was significantly higher in both EGC tissues (5.31 +/- 0.49 micro gram/mg protein, p<0.001) and AGC tissues (5.46 +/- 0.54 micro gram/mg protein, p<0.001) than in non-cancerous tissues of controls (4.22 +/- 0.8 micro gram/mg protein). There was no significant difference of 15d-PGJ2 concentration between gastric cancer tissues and controls. CONCLUSIONS: COX-2 overexpression and increased PGE2 concentration in gastric tissues may play an important role in gastric carcinogenesis. However, the role of PPAR (delta and gamma) and 15d-PGJ2 in gastric carcinogenesis is uncertain. Further studies are needed.