Gene expression profile in JNK3 null mice: a novel specific activation of the PI3K/AKT pathway.
JNK3 is mainly expressed in the CNS and it plays a crucial role in neuronal death in several neurodegenerative diseases. By contrast, the isoforms JNK1 and JNK2 seem to be involved in brain development. The lack of Jnk3 confers neuroprotection, although mechanisms responsible are unknown. The present study analyzes the gene expression profile in hippocampus from mice lacking Jnk3 in comparison to wild-type mice. The microarray analysis showed that 22 genes are differentially expressed (z-score>2 in two independent arrays) in Jnk3 null mice. Among these, we focused on pi3kcb, as it is directly related to the prosurvival phosphoinositide-3-kinase (PI3K)/AKT pathway. Results from Jnk3 null mice showed an increase in pik3cb transcript and protein, together with an increase in PI3K activity and phosphorylation of AKT. By contrast, these changes were not observed in Jnk1 null mice, which do not present neuroresistance to certain neurodegenerative insults. Therefore, our results indicate that the activation of PI3K/AKT pathway in hippocampus because of the increase in pik3cb transcription and that this mechanism is specifically related to the lack of Jnk3.
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Barcelona, Spain. felixjunyent@ub.edu
Fèlix
F
Junyent
Luisa
L
de Lemos
Ester
E
Verdaguer
Jaume
J
Folch
Isidre
I
Ferrer
Daniel
D
Ortuño-Sahagún
Carlos
C
Beas-Zárate
Rafael
R
Romero
Merce
M
Pallàs
Carme
C
Auladell
Antoni
A
Camins
D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000172:deficiency / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000172:deficiency; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018709:Statistics, Nonparametric
D048057:Mitogen-Activated Protein Kinase 10; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048055:Mitogen-Activated Protein Kinase 8