PHOSPHOINOSITIDE AND CALCIUM SIGNALING RESPONSES IN SMOOTH-MUSCLE CELLS - COMPARISON BETWEEN LIPOPROTEINS, ANG-II, AND PDGF

被引:51
作者
BOCHKOV, V
TKACHUK, V
BUHLER, F
RESINK, T
机构
[1] BASEL UNIV HOSP,DEPT RES,CH-4031 BASEL,SWITZERLAND
[2] ACAD MED SCI USSR,CARDIOL RES CTR,INST EXPTL CARDIOL,MOLEC ENDOCRINOL LAB,MOSCOW,USSR
关键词
D O I
10.1016/0006-291X(92)91372-W
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of low density lipoprotein (LDL) and high density lipoprotein (HDL3) on second messenger systems were investigated in cultured human vascular smooth muscle cells (VSMC) and compared with those of angiotensin II (Ang II) and platelet-derived growth factor (PDGF-BB). Phosphoinositide metabolism was studied in myo-[2-3H]-inositol prelabelled VSMC using high performance liquid anionexchange chromatography. The spectra of inositol phosphate isomers increased after stimulation with either Ang II, LDL, HDL3, or PDGF-BB were qualitatively identical. Major increases occurred in 4-IP1, 1,4-IP2, 1,3,4-IP3 and 1,3,4,5-IP4. These are metabolic conversion products of 1,4,5-IP3 for which only a minor increase was found. Thus lipoproteins, like Ang II and PDGF-BB, activate polyphosphatidylinositol-specific phospholipase C. Intracellular Ca2+ concentrations ([Ca2+]ii) were studied in fura-2 loaded VSMC. In monolayer cultures LDL and HDL3 increased [Ca2+]i with kinetics comparable to those for Ang II. Relative to the effects of these agonists, the PDGF-BB-induced increase in [Ca2+]i was slower in onset and the decay from peak [Ca2+]i levels more gradual. Fluorescence recordings from single cells exposed to LDL and HDL3 revealed a prolonged series of transient oscillations of [Ca2+]i, a phenomenon typical for calcium-mobilizing hormones. Additionally, as found for Ang II, preincubation of VSMC with either phorbol 12-myristate, 13-acetate, forskolin or 8-bromo-cyclic GMP inhibited LDL, and HDL-induced accumulation of [3H]-inositol monophosphate. We propose that LDL and HDL3 stimulate signal transduction in VSMC via mechanisms analogous to those of C2+-mobilizing hormones. © 1992.
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页码:1295 / 1304
页数:10
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