PMID- 19444281
OWN - NLM
STAT- MEDLINE
DCOM- 20091103
LR  - 20110719
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Linking)
VI  - 16
IP  - 9
DP  - 2009 Sep
TI  - Angiogenin protects motoneurons against hypoxic injury.
PG  - 1238-47
LID - 10.1038/cdd.2009.52 [doi]
AB  - 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.
FAU - Sebastia, J
AU  - Sebastia J
AD  - Department of Physiology and Medical Physics and RCSI Neuroscience Research 
      Centre, Royal College of Surgeons in Ireland, Dublin, Dublin 2, Ireland.
FAU - Kieran, D
AU  - Kieran D
FAU - Breen, B
AU  - Breen B
FAU - King, M A
AU  - King MA
FAU - Netteland, D F
AU  - Netteland DF
FAU - Joyce, D
AU  - Joyce D
FAU - Fitzpatrick, S F
AU  - Fitzpatrick SF
FAU - Taylor, C T
AU  - Taylor CT
FAU - Prehn, J H M
AU  - Prehn JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090515
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - EC 3.1.27.- (angiogenin)
RN  - EC 3.1.27.5 (Ribonuclease, Pancreatic)
SB  - IM
MH  - Amino Acid Substitution
MH  - Amyotrophic Lateral Sclerosis/genetics/*metabolism
MH  - Animals
MH  - Apoptosis
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Neurons/*metabolism
MH  - Mutation
MH  - RNA, Small Interfering/metabolism
MH  - Recombinant Proteins/metabolism/pharmacology
MH  - Ribonuclease, Pancreatic/genetics/*metabolism/pharmacology
MH  - Signal Transduction
MH  - Vascular Endothelial Growth Factors/metabolism
EDAT- 2009/05/16 09:00
MHDA- 2009/11/05 06:00
CRDT- 2009/05/16 09:00
PHST- 2009/05/16 09:00 [entrez]
PHST- 2009/05/16 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
AID - cdd200952 [pii]
AID - 10.1038/cdd.2009.52 [doi]
PST - ppublish
SO  - Cell Death Differ. 2009 Sep;16(9):1238-47. doi: 10.1038/cdd.2009.52. Epub 2009 
      May 15.