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  1. Article ; Online: Lipoprotein-associated phospholipase A2 as a predictive biomarker of sub-clinical inflammation in cardiovascular diseases.

    Cojocaru, Manole / Cojocaru, Inimioara Mihaela / Silosi, Isabela

    Maedica

    2011  Volume 5, Issue 1, Page(s) 51–55

    Abstract: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor biomarker for incident ... in atherosclerosis is still under investigation. Lp-PLA2 belongs to the superfamily of phospholipase A2 enzymes ... by lypophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. Phospholipase A2 plays ...

    Abstract Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor biomarker for incident atherosclerotic disease. Lp-PLA2 has been identified in atherosclerotic plaques, however, its role in atherosclerosis is still under investigation. Lp-PLA2 belongs to the superfamily of phospholipase A2 enzymes. It is produced by macrophages that appears to play a role in the atherosclerotic vessel wall. Emerging data seem to suggest that Lp-PLA2 may be proatherogenic, which is an effect thought to be mediated by lypophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. Phospholipase A2 plays an essential role in metabolism of membrane phospholipids, it is related to inflammatory reactions, secretion of amyloid precursor protein. Several studies have documented the strong association of Lp-PLA2 with coronary heart disease and stroke in the general population. Lp-PLA2 may be a stronger predictor of recurrent stroke risk. Inflammatory markers have been associated with ischemic stroke risk. Their relationship to prognosis after stroke is unsettled. The present review article focuses particularly on the characteristics of the Lp(a)-associated Lp-PLA2 and discusses the possible role of this enzyme in view of the new data.
    Language English
    Publishing date 2011-09-28
    Publishing country Romania
    Document type Journal Article
    ZDB-ID 2399972-X
    ISSN 2069-6116 ; 2069-6116
    ISSN (online) 2069-6116
    ISSN 2069-6116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The selective lipoprotein-associated phospholipase A2 inhibitor darapladib triggers irreversible actions on glioma cell apoptosis and mitochondrial dysfunction.

    Wang, Yun-Ju / Chang, Song-Bin / Wang, Chih-Yen / Huang, Hui-Ting / Tzeng, Shun-Fen

    Toxicology and applied pharmacology

    2020  Volume 402, Page(s) 115133

    Abstract: ... phospholipase A2 (Lp-PLA2) that is encoded by the PLA2G7 gene and serves as a predictive biomarker of sub ... clinical inflammation in cardiovascular diseases. The three glioma cell lines (rat C6 glioma cell line ... we evaluated the anti-glioma effects of darapladib, a selective reversible inhibitor of lipoprotein-associated ...

    Abstract Although the development of a therapeutic strategy for glioblastoma multiforme (GBM), the most aggressive type of brain tumor in adults, is in progress, the prognosis is still limited. In this study, we evaluated the anti-glioma effects of darapladib, a selective reversible inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) that is encoded by the PLA2G7 gene and serves as a predictive biomarker of sub-clinical inflammation in cardiovascular diseases. The three glioma cell lines (rat C6 glioma cell line, human U87MG, and human U251MG) and an ex vivo brain tissue slice-glioma cell co-culture system were used to validate the inhibitory effect of darapladib on the expansion of glioma cells. Exposure to darapladib at doses higher than 5 μM induced profound cytotoxicity in C6, U87MG, and U251MG. Moreover, the colony formation ability of the glioma cell lines was significantly repressed after the addition of darapladib. Although darapladib did not reduce the generation of the Lp-PLA2 downstream molecule, arachidonic acid (AA), in the glioma cells, this small compound triggered mitochondrial membrane depolarization and cell apoptosis in these glioma cells. In addition, transient exposure to darapladib induced the upregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) levels, but reduced phosphorylation of AKT/PKB (protein kinase B). The results from an ex vivo brain slice culture system further confirmed the effective inhibition of darapladib on the expansion of glioma cells. In conclusion, darapladib acts as a potential anti-glioma compound via the induction of mitochondrial membrane depolarization and cell apoptosis, and the inhibition of AKT signaling in glioma cells.
    MeSH term(s) Animals ; Antibodies ; Apoptosis/drug effects ; Benzaldehydes/pharmacology ; Brain/cytology ; Cell Cycle/drug effects ; Cell Line, Tumor ; Extracellular Signal-Regulated MAP Kinases/genetics ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Glioma ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Mitochondrial Diseases/drug therapy ; Oximes/pharmacology ; Phospholipase A2 Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Rats
    Chemical Substances Antibodies ; Benzaldehydes ; Oximes ; Phospholipase A2 Inhibitors ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; darapladib (UI1U1MYH09)
    Language English
    Publishing date 2020-07-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 204477-8
    ISSN 1096-0333 ; 0041-008X
    ISSN (online) 1096-0333
    ISSN 0041-008X
    DOI 10.1016/j.taap.2020.115133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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