W. Drobnik et al., INFLUENCE OF LIPOPROTEINS ON INTRACELLULA R SIGNAL-TRANSDUCTION IN HUMAN FIBROBLASTS, Nieren- und Hochdruckkrankheiten, 23(5), 1994, pp. 250-252
Lipoproteins induce signal transduction in human fibroblasts. Stimulat
ion with HDL3 or LDL result in a rapid activation of phosphatidylinosi
tol specific phospholipase C. This enzyme catalyses the degradation of
phosphatidylinositol-diphosphate (PIP2) to inositoltriphosphate (IP3)
and 1,2 diacylglycerol (1,2-DAG). Generation of IP3 leads to the rele
ase of calcium from intracellular stores and therefore causes a rise i
n cellular calcium concentration. The maximal effect was seen with con
centrations around 15 mug/ml HDL3 or LDL. The maximum increase of [Ca+]i was 480 nM after stimulation with LDL and 400 nM with HDL3. 1,2-DA
G as well as calcium are potent activators of protein kinase C. Accord
ingly, after stimulation with both lipoproteins we observed a transloc
ation of PKC(alpha) and PKC(epsilon) from the cytosol to the cell memb
rane, which reflect the activation of these kinases. In addition to th
e PLC pathway, both lipoproteins induce the adenylate cyclase signalli
ng pathway and cause an increase in intracellular cAMP concentration.
10 s after stimulation cAMP concentration increased from 1 pmol/mg cel
l protein to 10 pmol. The concentration returned to basal levels withi
n 30 s after stimulation with LDL and 120 s after incubation with HDL3
. A rise in cGMP concentration was only seen after stimulation with LD
L and not with HDL3. In summary the investigation of lipoprotein induc
ed signal transduction indicated potential mechanisms, by which HDL3 a
nd LDL might mediate their influence on various cell functions.