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  • Neuroprotection by leptin in a rat model of permanent cerebral ischemia: effects on STAT3 phosphorylation in discrete cells of the brain. 22158477

    In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ischemic cortex. The early enhancement of nuclear phospho-STAT3 induced by leptin in the astrocytes of the ischemic penumbra may contribute to a beneficial effect of these cells on the evolution of tissue damage. In addition, the elevation of phospho-STAT3 induced by leptin in the neurons after 24 h MCAo is associated with an increased expression of tissue inhibitor of matrix metalloproteinases-1 in the cortex, suggesting its possible involvement to the neuroprotection produced by the adipokine.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple
  • Regulation of pyruvate dehydrogenase kinase expression by the farnesoid X receptor. 15721319

    The pyruvate dehydrogenase complex (PDC) functions as an important junction in intermediary metabolism by influencing the utilization of fat versus carbohydrate as a source of fuel. Activation of PDC is achieved by phosphatases, whereas, inactivation is catalyzed by pyruvate dehydrogenase kinases (PDKs). The expression of PDK4 is highly regulated by the glucocorticoid and peroxisome proliferator-activated receptors. We demonstrate that the farnesoid X receptor (FXR; NR1H4), which regulates a variety of genes involved in lipoprotein metabolism, also regulates the expression of PDK4. Treatment of rat hepatoma cells as well as human primary hepatocytes with FXR agonists stimulates the expression of PDK4 to levels comparable to those obtained with glucocorticoids. In addition, treatment of mice with an FXR agonist significantly increased hepatic PDK4 expression, while concomitantly decreasing plasma triglyceride levels. Thus, activation of FXR may suppress glycolysis and enhance oxidation of fatty acids via inactivation of the PDC by increasing PDK4 expression.
    Document Type:
    Reference
    Product Catalog Number:
    17-610
    Product Catalog Name:
    Magna ChIP™ A - Chromatin Immunoprecipitation Kit
  • Immunoprecipitation against exogenous antigens in the zone of alpha-1, alpha-2 and beta-globulins--a new immune phenomenon 10658363

    According to data by H. Zhabilov serum fractions in the zone of alpha 1, alpha 2 and beta-globulins from healthy people form a characteristic precipitation curve in terms of structure and density with the TNP (thymus nuclear protein) and CNP (carcinoma nuclear protein) as antigens when tested in two-dimensional agarose-gel electrophoresis. The observed immune phenomenon has not so far, to the best of our knowledge, been reported in the scientific literature and has profound implications for fundamental and applied immunology. The object of the present study was to confirm Zhabilov's data and study the ontogenetic aspect of the problem. We used 45 sera of children from different age groups, of healthy adult controls, HIV-infected and cancer patients. The sera were tested against the following exoantigens: TNP (thymus nuclear protein), CNP (carcinoma nuclear protein-Viral Genetics Inc, LA), as well as against ST (staphylococcal toxin), SL (streptolysin) and LPS (lipopolysaccharide) from Gram-negative bacteria (National Center for Parasitic and Infectious Diseases, Sofia, Bulgaria). Two-dimensional electrophoresis was used modified after the protocol of UCLA chemical labs. The results of our study show that immediately following birth the precipitation curve is barely discernible reaching the normal shape following 1 month-5 years of age. The precipitation curve from HIV-infected sera and those of cancer patients is similar to that of newborns. The results from our unpublished observations with sera from other biologic species tested against the same antigens show similar results: no curve was observed in fish whereas the reaction was positive with frogs, birds, rabbits and other mammals. This confirmation of the basic biologic law of ontogenesis being a repetition of phylogenesis gives us reason to consider those fractions as participating in the immune maturation of organisms for acquired immune response. There exists a possibility that they might be part of the already known immunomediators or a stage in the transition from non-specific to specific immunoglobulins which have not lost their importance in immunogenesis. The lack of previous studies in this respect and the observation and confirmation of this reaction in two different labs underscore the importance of this new immune phenomenon.
    Document Type:
    Reference
    Product Catalog Number:
    17-295
    Product Catalog Name:
    Chromatin Immunoprecipitation (ChIP) Assay Kit
  • PA51/P11-SEV-MOL28340

    Document Type:
    Certificate of Quality
    Lot Number:
    MOL28340
    Product Catalog Number:
    PA51/P11-SEV
    Product Catalog Name:
    NovAseptic Valve, Inductive Position Indicator Unit, Namur