1,720,974 research outputs found

    Sphingolipid metabolites in neural signalling and function

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    Sphingolipid metabolites, such as ceramide, sphingosine, sphingosine-1-phosphate (S1P) and complex sphingolipids (gangliosides), are recognized as molecules capable of regulating a variety of cellular processes. The role of sphingolipid metabolites has been studied mainly in non-neuronal tissues. These studies have underscored their importance as signals transducers, involved in control of proliferation, survival, differentiation and apoptosis. In this review, we will focus on studies performed over the last years in the nervous system, discussing the recent developments and the current perspectives in sphingolipid metabolism and functions

    Role of mitochondria in serum withdrawal-induced apoptosis of immortalized neuronal precursors

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    Abstract The intracellular mechanisms controlling apoptosis in immature neurons are still largely unknown. Taking immortalized hippocampal neuronal precursors (mouse cell line HN9.10e) as a model, we have analyzed the cellular events associated to apoptosis induced by serum deprivation. We observed translocation of Bax from cytosol to mitochondria after 1 h of serum withdrawal followed, 2 h later, by cytochrome c release from mitochondria. These events occurred without mitochondrial membrane potential loss nor mitochondrial calcium raise. As calcium is implicated in several cell death pathways, we analyzed intracellular calcium levels after longer periods of 21 21 serum deprivation. After 6 h, an increase of cytosolic Ca was detected in HN9.10e cells loaded with the Ca indicator Fluo3-AM. This increase of calcium preceded morphological signs of apoptosis such as cell shrinkage and nuclear fragmentation, and was followed by a more pronounced raise that persisted until the terminal phases of the apoptotic process. Cells serum-deprived for 4 h and then grown in complete medium for 20 h fully recovered viability. Summarizing, in HN9.10e cells, calcium deregulation occurs in the late phases of apoptosis; earlier events involve translocation of Bax, release of cytochrome c, and maintenance of mitochondrial functionality. This allows an enlargement of the temporal window in which commitment to death is reversible
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