Endothelin-1 induces degeneration of cultured motor neurons: underlying mechanisms (Abstract/Poster in atti di convegno)

Type
Label
  • Endothelin-1 induces degeneration of cultured motor neurons: underlying mechanisms (Abstract/Poster in atti di convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Simona D'Antoni1, Eugenia Ranno1, Maria Vincenza Catania1,2 (2014)
    Endothelin-1 induces degeneration of cultured motor neurons: underlying mechanisms
    in 9th FENS Forum of Neuroscience ., Milano, 05-09/07/2014
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Simona D'Antoni1, Eugenia Ranno1, Maria Vincenza Catania1,2 (literal)
Note
  • Poster (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Institute of Neurological Sciences, National Research Council (ISN-CNR), via P. Gaifami 18, 95126 Catania, Italy. 2IRCCS Oasi Maria SS, Troina (EN), Italy. (literal)
Titolo
  • Endothelin-1 induces degeneration of cultured motor neurons: underlying mechanisms (literal)
Abstract
  • AIMS: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons (MNs) and astrogliosis. Factors secreted by activated astrocytes might contribute to MN degeneration. We focused on endothelin-1 (ET-1), a peptide strongly up-regulated in reactive astrocytes under pathological conditions. We have previously found that ET-1 i) is abundantly expressed by reactive astrocytes in the spinal cord of SOD-1 G93A mice and ALS patients and ii) exerts a toxic effect on cultured MNs through activation of astrocytic ET receptors (Ranno et al., 2014). The present study is aimed at identifying the mechanisms underlying ET-1 toxicity. We focused on cell survival pathways, such as phosphatidylinositide 3-kinase (PI3K) pathway and/or inflammatory processes. METHODS: Mixed spinal cord cultures were treated with ET-1 (100 nM for 48 h) with/without LPS (40 ng/ml) or inhibitors of PI3K (LY294002 50 µM) and nitric oxide (NO) synthase (L-NAME 40µM). We performed immunocytochemistry using SMI-32 antibody(Sternberger Monoclonal) to label MNs and counted the number of surviving MNs after treatments. RESULTS: Inhibition of PI3K pathway caused MN death, as expected; however, exposure to ET-1 in the presence of LY294002 did not result in a further increase of MN death. Similarly, LPS induced MN death but its effect was not additive with that of ET-1. Furthermore, the effect of ET-1 was not reversed by L-NAME. CONCLUSIONS: ET-1 may cause neuronal death by a mechanism that involves the PI3K pathway. An inflammatory component may account for the ET-1 toxicity, but does not involve NO production. (literal)
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