Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content

Marco Racchi, Roberta Baetta, Nathalie Salvietti, Paola Ianna, Guido Franceschini, Rodolfo Paoletti, Remo Fumagalli, Stefano Govoni, Marco Trabucchi, Maurizio Soma

Research output: Contribution to journalArticle

Abstract

Plasma-membrane composition plays a crucial role in most of the cellular functions that depend on membrane processes. In virtually all cell types the proteolytic processing of Alzheimer amyloid precursor protein (APP) to generate soluble APP (sAPP) is believed to occur at the plasma membrane or in its immediate proximity. Alteration of this metabolic pathway has been linked to the pathogenesis of Alzheimer's disease. We analysed the effect of membrane cholesterol enrichment on APP metabolism. Incubation of COS cells with increasing concentrations of non-esterified cholesterol carried by rabbit β-very low-density lipoprotein caused a dose-dependent inhibition of sAPP release: 70% inhibition with 10 μg/ml non-esterified cholesterol. A less pronounced inhibitory effect was observed on treatment with human low-density lipoprotein. Inhibition of sAPP release was independent of receptor-mediated lipoprotein metabolism since simultaneous treatment with chloroquine did not modify the effect of lipoprotein treatment. In addition, treatment with cholesterol dissolved in either ethanol or methyl-β-cyclodextrin elicited the same effect. Excess non-esterified cholesterol did not cause cell toxicity. Cell cholesterol mass inversely correlated with sAPP release. Progesterone, which inhibits shuttling of nonesterified cholesterol between the plasma membrane and intracellular pools, had no effect on the inhibition of sAPP release from cholesterol-loaded cells, providing indirect evidence that cholesterol may act at the plasma membrane.

Original languageEnglish
Pages (from-to)893-898
Number of pages6
JournalBiochemical Journal
Volume322
Issue number3
Publication statusPublished - Mar 15 1997

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Amyloid beta-Protein Precursor
Cholesterol
Processing
Cell membranes
Cell Membrane
Metabolism
Lipoproteins
Lipoprotein Receptors
Membranes
VLDL Lipoproteins
COS Cells
Chloroquine
Cyclodextrins
Metabolic Networks and Pathways
LDL Lipoproteins
Progesterone
Toxicity
Alzheimer Disease
Ethanol
Rabbits

ASJC Scopus subject areas

  • Biochemistry

Cite this

Racchi, M., Baetta, R., Salvietti, N., Ianna, P., Franceschini, G., Paoletti, R., ... Soma, M. (1997). Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content. Biochemical Journal, 322(3), 893-898.

Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content. / Racchi, Marco; Baetta, Roberta; Salvietti, Nathalie; Ianna, Paola; Franceschini, Guido; Paoletti, Rodolfo; Fumagalli, Remo; Govoni, Stefano; Trabucchi, Marco; Soma, Maurizio.

In: Biochemical Journal, Vol. 322, No. 3, 15.03.1997, p. 893-898.

Research output: Contribution to journalArticle

Racchi, M, Baetta, R, Salvietti, N, Ianna, P, Franceschini, G, Paoletti, R, Fumagalli, R, Govoni, S, Trabucchi, M & Soma, M 1997, 'Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content', Biochemical Journal, vol. 322, no. 3, pp. 893-898.
Racchi M, Baetta R, Salvietti N, Ianna P, Franceschini G, Paoletti R et al. Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content. Biochemical Journal. 1997 Mar 15;322(3):893-898.
Racchi, Marco ; Baetta, Roberta ; Salvietti, Nathalie ; Ianna, Paola ; Franceschini, Guido ; Paoletti, Rodolfo ; Fumagalli, Remo ; Govoni, Stefano ; Trabucchi, Marco ; Soma, Maurizio. / Secretory processing of amyloid precursor protein is inhibited by increase in cellular cholesterol content. In: Biochemical Journal. 1997 ; Vol. 322, No. 3. pp. 893-898.
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