Vn. Bochkov et al., HORMONE-LIKE EFFECTS OF PLASMA-LIPOPROTEINS ON HUMAN PLATELETS AND VASCULAR SMOOTH-MUSCLE CELLS, Biochemistry, 59(7), 1994, pp. 715-720
The fluorescent Ca2+-sensitive probes Quin 2 and Fura 2 were used to s
tudy plasma lipoprotein-induced transients of cytosolic calcium, [Ca2](4,)(i) in washed human platelets and cultured smooth muscle cells fr
om human aorta. With both types of cells HDL(3) and LDL were shown to
induce rapid and reversible increase in [Ca2+](i) levels. The effects
were dose-dependent and attained saturation at physiological HDL(3) an
d LDL in concentrations. The lipoproteins were also capable of stimula
ting phosphoinositides turnover, with the resulting accumulation of DA
G, IP1, IP2, and IP3. HPLC analysis of inositol phosphate isomers demo
nstrated that LDL and HDL(3) activated the polyphosphoinositide-specif
ic phospholipase C. These data were suggestive of lipoprotein similari
ty to aggregation inducers and vasoactive hormones, which activate sec
ond messenger systems in platelets and smooth muscle cells, respective
ly. The hormone-like effects of lipoproteins on the cells were inhibit
ed by protein kinase C activators, as well as by agents capable of sti
mulating cAMP- and cGMP-dependent protein kinases. The lipoprotein-ind
uced [Ca2+](i) elevation was significantly attenuated if the smooth mu
scle cells were pretreated by Bordetella pertussis toxin. In contrast,
LDL-induced [Ca2+](i) increase was 2 to 3 times more pronounced in th
e presence of epinephrine; The results indicate that the mechanisms wh
ereby hormones and lipoproteins activate phosphoinositides turnover ar
e similar and may involve G-proteins.