High-density lipoproteins induce a rapid and transient release of Ca2+ in cultured fibroblasts

Abstract

Several different cell types showed increased rates of proliferation and cholesterol mobilization in response to treatment with high-density lipoprotein (HDL). This would suggest that one main function of HDL is the activation of signal pathways in cells. In the current study we have used the fluorescent indicator fura-2 to monitor the level of cytosolic Ca2l ([Ca2+]

LPA receptor signaling: pharmacology, physiology, and pathophysiology

“…However, there is a growing range of recognized chemical forms of LPA in various biological systems (31,32) that have been observed in concentrations spanning low nanomolar to micromolar levels. LPA concentrations in blood can range from 0.1 M in plasma and up to 10 M in serum, which is well over the apparent nanomolar K d of LPA [1][2][3][4][5][6] (23,(33)(34)(35) (36)(37)(38). Aside from blood, LPA has been quantifi ed in a variety of species, tissues, and fl uids, including neural tissue, cerebrospinal fl uid (CSF), seminal fl uid, urine, saliva, and aqueous humor (7,36,(39)(40)(41)(42)(43)(44)(45) (Table 1).…”

“…This fi nding has been supported by secondary readouts of receptor activity, because direct confi rmation through classical receptor binding studies has been diffi cult. 6 . Ranges of compound EC 50 , IC 50 , or K i values are given on the x axis, progressing from strong antagonism on the left to strong agonism on the right.…”

“…Two other LPA receptors, LPA 2 and LPA 3 , were subsequently discovered based on shared homology with LPA 1 . In the past ten years, three additional LPA receptors have been discovered (LPA [4][5][6] ) (19)(20)(21)(22)(23) that are members of the P2Y purinergic family (Fig. 1).…”

“…The diverse and numerous physiological effects of LPA are mediated through six currently recognized LPA receptors, LPA [1][2][3][4][5][6] : protein names LPA 1 -LPA 6 and gene names LPAR1-LPAR6 (human) and Lpar1-Lpar6 (nonhuman) (11,83). These 7-TM GPCRs couple to at least one or more of the four G ␣ proteins (G 12/13 , G q/11 , G i/o , and G s ) that initiate a variety of signaling cascades.…”

High Density Lipoproteins and Arteriosclerosis

“…DAG activates PKC, which has been shown to stimulate the translocation of newly synthesized cholesterol to the plasma membrane as well as cholesterol efflux. 95,96,104,108 By contrast, HDL-mediated breakdown of phosphatidylinositol biphosphate and the subsequent mobilization of intracellular calcium 106,109 does not stimulate cholesterol efflux but rather mediates the mitogenic effects of HDL. 110 In macrophages, HDL has been shown to increase the concentration of cAMP, resulting in the activation of protein kinase A, which may activate the hydrolysis of cytosolic cholesteryl esters by NCEH and the mobilization of cholesterol by ABC1.…”