Partial characterization of apoptotic factor in alzheimer
plasma.
Maesaka, John K., Thomas Palaia, Soheli A. Chowdhury, Tetsuo
Shimamura, Steven Fishbane, William Reichman, Andrew Coyne, Julian J.
O'rear and Marwan E. El-Sabban,.
1Department of Medicine, Winthrop-University Hospital, Mineola,
N.Y. 11501, 2Departments of Pathology, 3Geriatric Services, Robert
Wood Johnson Medical School, Piscataway, N.J. 08854, and 4Department
of Human Morphology, American University, Beirut, Lebanon
APStracts 5:0189F, 1998.
We previously demonstrated that a plasma natriuretic factor is present
in Alzheimer's disease (AD) but not in multi-infarct dementia (MID)
or normal controls (C). We postulated that the natriuretic factor
might induce the increased cytosolic calcium reported in AD by
inhibiting the sodium-calcium antiporter, thereby activating the
apoptotic pathway. To test for a factor in AD plasma that induces
apoptotsis, we exposed nonconfluent cultured LLC-PK1 cells to plasma
from AD, MID and C for 2 h and performed a TUNEL assay. The plasma
from AD increased apoptosis nearly fourfold as compared to MID and C.
The effect was dose-dependent and the peak effect was attained after
a 2 h exposure. Additionally, apoptotic morphology was detected by
electron microscopy and internucleosomal DNA cleavage found.
Apoptosis was inhibited by removing calcium from the medium,
inhibiting protein synthesis with cycloheximide, boiling or
alternately freezing and thawing the plasma and digesting a partially
purified fraction with trypsin. Heating AD plasma to 56( C did not
deactivate the apoptotic factor. These results demonstrate an
apoptotic factor present in the plasma of patients with AD.
Received 14 October 1997; accepted in final form 22 October 1998
APS Manuscript Number F329-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998