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Jochen HM Prehn
C T Taylor
S F Fitzpatrick
D Joyce
D F Netteland
M A King
B Breen
D Kieran
J SebastiĆ 



signal transduction transgenic physics rna small interfering ribonuclease pancreatic ribonuclease rna mutation pancreatic motor neurons physiology apoptosis mice transgenic animals cells cultured cell hypoxia mice amino acid substitution hypoxia inducible factor 1 alpha subunit small interfering amyotrophic lateral sclerosis vascular endothelial growth factors cells hypoxia inducible factor 1 alpha subunit recombinant proteins cultured

Angiogenin protects motoneurons against hypoxic injury. (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-1alpha 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, C T Taylor, S F Fitzpatrick, D Joyce, D F Netteland, M A King, B Breen, D Kieran, J SebastiĆ 

Experts in our system

Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Cormac T. Taylor
University College Dublin
Total Publications: 110
Susan F. Fitzpatrick
University College Dublin
Total Publications: 9