Altered response of fibroblasts from aged and Alzheimer donors to drugs that elevate cytosolic free calcium.
Previous studies demonstrate that resting intracellular calcium in cultured skin fibroblasts declines due to in vivo aging and is further depressed by Alzheimer's disease. These data suggest that altered calcium homeostasis may underlie the deficits in cell function (e.g., cell spreading) that also occur in these cells. Depressed cytosolic free calcium in fibroblasts from aged and Alzheimer donors can be elevated by various drug treatments. 3,4-Diaminopyridine, serum, N-formyl-methionyl-leucyl-phenylalanine and bradykinin increased cytosolic free calcium transiently although the rate of the increase was slower and the magnitude of the rise was less in cells from aged and Alzheimer donors when compared to young donors. Four minutes after N-formyl-methionyl-leucyl-phenylalanine or bradykinin treatment cytosolic free calcium returned to resting levels in all six cell lines. Six minutes after either serum or 3,4-diaminopyridine treatments, however, cytosolic free calcium in cells from aged and Alzheimer donors remained elevated at concentrations similar to the resting calcium level in young cells. Bradykinin and serum were effective in the absence of extracellular calcium but 3,4-diaminopyridine and N-formyl-methionyl-leucyl-phenylalanine were not. These demonstrate that dynamic, as well as resting calcium homeostasis, is altered in cultured skin fibroblasts from aged and Alzheimer donors.
Peterson
C
C
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Ratan
R R
RR
Shelanski
M L
ML
Goldman
J E
JE
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012867:Skin / Q000378:metabolism
D000631:Aminopyridines; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015761:4-Aminopyridine; D000077770:Amifampridine; D001920:Bradykinin; D002118:Calcium