Abstract
High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues. Although their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. To this aim, we investigated the replicative cycles in synchronised Swiss 3T3 fibroblasts in different experimental conditions: i) contact-inhibited fibroblasts re-entering cell cycle after dilution; ii) scratch-wound assay; iii) serum-deprived cells induced to re-enter G1 by FCS, HDL or PDGF. Analyses were performed during each cell cycle up to quiescence. Cholesterol synthesis increased remarkably during the replicative cycles, decreasing only after cells reached confluence. In contrast, cholesteryl ester (CE) synthesis and content were high at 24 h after dilution and then decreased steeply in the successive cycles. Flow cytometry analysis of DiO-HDL, as well as radiolabeled HDL pulse, demonstrated a significant uptake of CE-HDL in 24 h. DiI-HDL uptake, lipid droplets (LDs) and SR-BI immunostaining and expression followed the same trend. Addition of HDL or PDGF partially restore the proliferation rate and significantly increase SR-BI and pAKT expression in serum-deprived cells. In conclusion, cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs.
Highlights
High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues
We report that the passage of quiescent normal fibroblasts to the replicative cycle presents peculiar modifications of CE metabolism, where HDL plays a major role in regulating CE content
This protein generally removes excess cholesterol from peripheral cells and delivers it to HDL, its role is devoted to catching preformed CEs in specialised organs, where storage of cholesterol is needed for hormone or bile acid synthesis[20,21]
Summary
High density lipoproteins (HDLs) play a crucial role in removing excess cholesterol from peripheral tissues Their concentration is lower during conditions of high cell growth rate (cancer and infections), their involvement during cell proliferation is not known. Cell transition from G0 to G1/S requires CE-HDL uptake, leading to CE-HDL/SR-BI pathway activation and CEs increase into LDs. A high rate of cholesterol synthesis, uptake and esterification in proliferating tissues, accompanied by reduction of plasma cholesterol-HDL, has been extensively described during tumour growth[1,2,3,4,5,6]. We investigated CE metabolism during the growth of synchronised mouse 3T3 fibroblasts
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