Inositol phosphates and intracellular calcium after bradykinin stimulation in fibroblasts from young, normal aged and Alzheimer donors.
Several studies suggest that alterations in the receptor-mediated phosphoinositide cascade and cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease. Therefore, the phosphoinositide cascade and [Ca2+]i were determined under resting conditions and after stimulation with bradykinin (100 nM) in cultured human skin fibroblasts from young (21 +/- 3 years), normal aged (59 +/- 6 years) and Alzheimer subjects (58 +/- 6 years). The inositol polyphosphates (IP3, IP2 and IP) were monitored after prelabeling the cells with [3H]inositol in serum free medium. [Ca2+]i was determined with the fluorescent probe, fura-2AM, under exactly analogous conditions. The bradykinin-induced formation of IP3 and IP2 increased significantly in fibroblasts from normal aged and Alzheimer donors compared to young subjects, but did not differ from each other. Bradykinin-induced IP3 formation was 63-117% above the young group at time points between 10-60 s in normal aged or Alzheimer donors. Bradykinin-induced IP2 formation was 49-59% above the young group at time points between 10-60 s in normal aged or Alzheimer subjects. Neither the basal [Ca2+]i, nor the bradykinin-stimulated [Ca2+]i, differed among fibroblasts from young, normal aged and Alzheimer donors. The precise molecular basis and pathophysiological significance of the enhanced bradykinin-induced phosphoinositide cascade in fibroblasts from aged donors remains to be determined.
Huang
H M
HM
Burke Medical Research Institute, Department of Neurology and Neuroscience, Cornell University Medical College, White Plains, NY 10605.
Toral-Barza
L
L
Thaler
H
H
Tofel-Grehl
B
B
Gibson
G E
GE
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D008875:Middle Aged; D013268:Stimulation, Chemical
D007295:Inositol Phosphates; D001920:Bradykinin; D002118:Calcium