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Correspondence to:
John F. Oram
High density lipoprotein (HDL) phospholipids and apolipoproteins remove cellular lipids by two distinct mechanisms, but their relative contribution to reverse cholesterol transport is unknown. Whereas phospholipid-mediated cholesterol efflux from cultured cells reflects the activity of the HDL receptor SR-BI, apolipoprotein-mediated lipid removal is regulated in response to changes in cellular cholesterol content (positive) and cell proliferation rates (negative). Here we show that immortalization of human skin fibroblast lines with the papillomavirus E6/E7 oncogenes increased their proliferation rates and selectively reduced the activity of the apolipoprotein-mediated lipid removal pathway. This reduction was accompanied by a decrease in cellular cAMP levels and was reversed by treatment with a cAMP analog. The stimulatory effect of cAMP was independent of changes in cellular phenotype or activities of cholesteryl ester cycle enzymes. The severely impaired apolipoprotein-mediated lipid removal pathway in Tangier disease fibroblasts, which persisted after immortalization, was not improved by treatment with a cAMP analog, implying that the cellular defect in Tangier disease is upstream from this cAMP-dependent signaling pathway.
These results indicate that papillomavirus-induced immortalization of fibroblasts selectively reduces the activity of the apolipoprotein-mediated lipid removal pathway by a cAMP-dependent process, perhaps to prevent loss of cellular lipids needed for continual membrane synthesis.—Oram, J. F., A. J. Mendez, J. Lymp, T. J. Kavanagh, and C. L. Halbert. Reduction in apolipoprotein-mediated removal of cellular lipids by immortalization of human fibroblasts and its reversion by cAMP: lack of effect with Tangier disease cells. J. Lipid Res. 1999. 40: 1769;–1781.
Supplementary key words:
cholesterol efflux, phospholipid efflux, high density lipoprotein, apolipoproteins, immortalized cells, Tangier disease
Copyright © 1999 by Lipid Research, Inc.
Original Article
Reduction in apolipoprotein-mediated removal of cellular lipids by immortalization of human fibroblasts and its reversion by cAMP: lack of effect with Tangier disease cells
John F. Orama,
Armando J. Mendezd,
James Lympb,
Terrance J. Kavanaghc, and
Christine L. Halberte
a Departments of Medicine (Box 356426), University of Washington, Seattle, WA 98195
b Biostatistics, University of Washington, Seattle, WA 98195
c Environmental Health, University of Washington, Seattle, WA 98195
d Diabetes Research Institute, University of Miami School of Medicine, Miami, FL 33101
e Fred Hutchinson Cancer Research Center, Seattle, WA 98104
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