JNK contributes to Hif-1alpha regulation in hypoxic neurons.
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-1alpha, 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-1alpha 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-1alpha upregulation, probably via a direct interaction with the Hif-1alpha protein.
Antoniou
Xanthi
X
Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20157 Milano, Italy.
Sclip
Alessandra
A
Ploia
Cristina
C
Colombo
Alessio
A
Moroy
Gautier
G
Borsello
Tiziana
T
D000375:Aging / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology* / Q000473:pathology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D048031:JNK Mitogen-Activated Protein Kinases