Background
Phosphoinositide 3-kinase (PI3-K) signaling plays a crucial role in neuronal growth
and plasticity. Recently, we demonstrated that suicide brain is associated with decreased
activation and expression of selective catalytic and regulatory subunits of PI3-K.
The present investigation examined the regulation and functional significance of compromised
PI3-K in suicide brain at the level of upstream phosphatase and tensin homologue on
chromosome ten (PTEN) and downstream substrates 3-phosphoinositide-dependent kinase
1 (PDK1) and Akt.
Methods
Messenger RNA expression of Akt1, Akt3, PTEN, and PDK1 by competitive reverse transcription
polymerase polymerase chain reaction; protein expression of Akt1, Akt3, PTEN, PDK1,
phosphorylated Akt1 (Ser473 and Thr308), phosphorylated PDK1, and phosphorylated PTEN
by Western blot; and catalytic activities of Akt1, Akt3, and PDK1 by enzymatic assays
were determined in prefrontal cortex and hippocampus obtained from suicide subjects
and nonpsychiatric control subjects.
Results
No significant changes in the expression of Akt1 or Akt3 were observed; however, catalytic
activity of Akt1, but not of Akt3, was decreased in prefrontal cortex and hippocampus
of suicide subjects, which was associated with decreased phosphorylation of Akt1 at
Ser473 and Thr308. The catalytic activity of PDK1 and the level of phosphorylated
PDK1 were also decreased in both brain areas without any change in expression levels
of PDK1. On the other hand, messenger RNA and protein expression of PTEN was increased,
whereas the level of phosphorylated PTEN was decreased.
Conclusions
Our study demonstrates abnormalities in PI3-K signaling at several levels in brain
of suicide subjects and suggests the possible involvement of aberrant PI3-K/Akt signaling
in the pathogenic mechanisms of suicide.
Key Words
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Article info
Publication history
Published online: February 18, 2010
Accepted:
December 6,
2009
Received in revised form:
December 2,
2009
Received:
July 13,
2009
Identification
Copyright
© 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
