کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4178551 1276503 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation in Activation and Expression of Phosphatase and Tensin Homolog on Chromosome Ten, Akt1, and 3-Phosphoinositide-Dependent Kinase 1: Further Evidence Demonstrating Altered Phosphoinositide 3-Kinase Signaling in Postmortem Brain of Suicide Subject
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Modulation in Activation and Expression of Phosphatase and Tensin Homolog on Chromosome Ten, Akt1, and 3-Phosphoinositide-Dependent Kinase 1: Further Evidence Demonstrating Altered Phosphoinositide 3-Kinase Signaling in Postmortem Brain of Suicide Subject
چکیده انگلیسی

BackgroundPhosphoinositide 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.MethodsMessenger 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.ResultsNo 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.ConclusionsOur 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 67, Issue 11, 1 June 2010, Pages 1017–1025
نویسندگان
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