TY - JOUR
T1 - JNK contributes to Hif-1α regulation in hypoxic neurons
AU - Antoniou, Xanthi
AU - Sclip, Alessandra
AU - Ploia, Cristina
AU - Colombo, Alessio
AU - Moroy, Gautier
AU - Borsello, Tiziana
PY - 2010/1
Y1 - 2010/1
N2 - Hypoxia is an established factor of neurodegeneration. Nowadays, attention is directed at understanding how alterations in the expression of stress-related signaling proteins contribute to age dependent neuronal vulnerability to injury. The purpose of this study was to investigate how Hif-1α, a major neuroprotective factor, and JNK signaling, a key pathway in neurodegeneration, relate to hypoxic injury in young (6DIV) and adult (12DIV) neurons. We could show that in young neurons as compared to mature ones, the protective factor Hif-1α is more induced while the stress protein phospho-JNK displays lower basal levels. Indeed, changes in the expression levels of these proteins correlated with increased vulnerability of adult neurons to hypoxic injury. Furthermore, we describe for the first time that treatment with the D-JNKI1, a JNK-inhibiting peptide, rescues adult hypoxic neurons from death and contributes to Hif-1α upregulation, probably via a direct interaction with the Hif-1α protein.
AB - Hypoxia is an established factor of neurodegeneration. Nowadays, attention is directed at understanding how alterations in the expression of stress-related signaling proteins contribute to age dependent neuronal vulnerability to injury. The purpose of this study was to investigate how Hif-1α, a major neuroprotective factor, and JNK signaling, a key pathway in neurodegeneration, relate to hypoxic injury in young (6DIV) and adult (12DIV) neurons. We could show that in young neurons as compared to mature ones, the protective factor Hif-1α is more induced while the stress protein phospho-JNK displays lower basal levels. Indeed, changes in the expression levels of these proteins correlated with increased vulnerability of adult neurons to hypoxic injury. Furthermore, we describe for the first time that treatment with the D-JNKI1, a JNK-inhibiting peptide, rescues adult hypoxic neurons from death and contributes to Hif-1α upregulation, probably via a direct interaction with the Hif-1α protein.
KW - HIF-1α
KW - Hypoxia
KW - JNK
KW - Neurons
UR - http://www.scopus.com/inward/record.url?scp=75749132817&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=75749132817&partnerID=8YFLogxK
U2 - 10.3390/molecules15010114
DO - 10.3390/molecules15010114
M3 - Article
C2 - 20110876
AN - SCOPUS:75749132817
VL - 15
SP - 114
EP - 127
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 1
ER -