Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study.
BACKGROUND
Teenage suicide is a major public health concern. Although there is some understanding of the psychosocial factors associated with teenage suicide, little is known about the neurobiologic factors of teenage suicide. Protein kinase C (PKC) is a critical phosphorylating enzyme in the phosphoinositide signaling pathway (which is involved in many physiologic functions in the brain and has been implicated in the pathogenesis of mood disorders) and is also a target for the therapeutic action of mood-stabilizing drugs.


OBJECTIVE
To examine whether the pathogenesis of teenage suicide is associated with changes in PKC.


METHODS
Postmortem brain study.


METHODS
Seventeen teenage suicide victims and 17 nonpsychiatric control subjects.


METHODS
Catalytic activity of PKC and protein and messenger RNA levels of various PKC isozymes, such as PKC alpha, beta, and gamma, were determined in the prefrontal cortex and hippocampus of both groups.


RESULTS
Protein kinase C activity was statistically significantly decreased in membrane and cytosol fractions of the prefrontal cortex and hippocampus of teenage suicide victims compared with control subjects. Statistically significant decreases in protein levels of PKC alpha, beta I, beta II, and gamma isozymes were also observed in both of these fractions. These decreases were associated with decreases in levels of their respective messenger RNAs.


CONCLUSIONS
Because many physiologic functions are mediated through phosphorylation by PKC and because PKC is a target for the therapeutic action of psychoactive drugs, our findings indicate that the pathogenesis of teenage suicide may be associated with abnormalities in PKC and that PKC may be a target for therapeutic intervention in patients with suicidal behavior.
Pandey
Ghanshyam N
GN
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 60612, USA. Gnpandey@psych.uic.edu
Dwivedi
Yogesh
Y
Rizavi
Hooriyah S
HS
Ren
Xinguo
X
Conley
Robert R
RR
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002384:Catalysis; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D013405:Suicide / Q000706:statistics & numerical data*
D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C; D010751:Phosphopyruvate Hydratase