Angiogenin protects motoneurons against hypoxic injury
|Title:||Angiogenin protects motoneurons against hypoxic injury||Authors:||Sebasti, J.
|Permanent link:||http://hdl.handle.net/10197/5023||Date:||15-May-2009||Abstract:||Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1α is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS.||Type of material:||Journal Article||Publisher:||Nature Publishing Group||Copyright (published version):||2009 Nature Publishing Group||Keywords:||ALS;angiogenin;HIF-1α;hypoxia;motoneuron||DOI:||10.1038/cdd.2009.52||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||SBI Research Collection|
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