Type

Journal Article

Authors

J H M Prehn
C T Taylor
S F Fitzpatrick
D Joyce
B Breen
D F Netteland
D Kieran
M A King
J Sebastià
J. Sebasti

Subjects

Biochemistry

Topics
cell hypoxia hypoxia hypoxia inducible factor 1 alpha subunit hif 1 amyotrophic lateral sclerosis angiogenin vascular endothelial growth factors apoptosis animals mice amino acid substitution cells cultured hypoxia inducible factor hif mice transgenic rna small interfering ribonuclease pancreatic motoneuron als mutation recombinant proteins genetics signal transduction metabolism hypoxia inducible factor 1 motor neurons pharmacology

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-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.
Collections Ireland -> University College Dublin -> Systems Biology Ireland
Ireland -> University College Dublin -> Institutes and Centres
Ireland -> University College Dublin -> SBI Research Collection

Full list of authors on original publication

J H M Prehn, C T Taylor, S F Fitzpatrick, D Joyce, B Breen, D F Netteland, D Kieran, M A King, J Sebastià, J. Sebasti

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
3
Susan F. Fitzpatrick
University College Dublin
Total Publications: 9