Protein kinase C-zeta activity but not level is decreased in Alzheimer's disease microvessels.
While there is considerable evidence demonstrating altered activity of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer disease (AD) brains, little is known about the activity and/or levels of the atypical PKC isoforms. The objective of this study is to compare PKC-zeta activity and level in cerebral microvessels isolated from AD brains with microvessels from the brains of nondemented age-matched controls. Measurements of the kinase activity reveals that the PKC-zeta activity is significantly (P < 0.01) lower in AD brain microvessels compared with vessels from control brain. Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data demonstrate significant and divergent changes in the PKC-zeta activity and level in the microcirculation of the AD brain and suggest that aberrant regulation of microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at the blood-brain barrier in the AD brain.
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
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P
Moore
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J
White
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V
Christiansen
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P
Grammas
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D003720:Densitometry; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008833:Microcirculation / Q000201:enzymology; D008970:Molecular Weight; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000097:blood*; D000099221:Protein Kinase C zeta
D007527:Isoenzymes; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta