The intracellular quality control system down-regulates the secretion of amyloidogenic apolipoprotein A-I variants: a possible impact on the natural history of the disease

Biochimica Et Biophysica Acta
Marta MarchesiVittorio Bellotti

Abstract

Hereditary systemic amyloidosis caused by apolipoprotein A-I variants is a dominantly inherited disease characterised by fibrillar deposits mainly localized in the kidneys, liver, testis and heart. We have previously shown that the apolipoprotein A-I variant circulates in plasma at lower levels than the wild-type form (Mangione et al., 2001; Obici et al., 2004) thus raising the possibility that the amyloid deposits could sequester the circulating amyloidogenic chain or that the intracellular quality control can catch and capture the misfolded amyloidogenic chain before the secretion. In this study we have measured plasma levels of the wild-type and the variant Leu75Pro apolipoprotein A-I in two young heterozygous carriers in which tissue amyloid deposition was still absent. In both cases, the mutant was present at significantly lower levels than the wild-type form, thus indicating that the low plasma concentration of the apolipoprotein A-I variant is not a consequence of the protein entrapment in the amyloid deposits. In order to explore the cell secretion of amyloidogenic apolipoprotein A-I variants, we have studied COS-7 cells expressing either wild-type apolipoprotein A-I or two amyloidogenic mutants: Leu75Pro and Leu174Ser....Continue Reading

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Citations

Apr 5, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Monica GomaraschiLaura Calabresi
Oct 30, 2016·FEBS Letters·Angela ArcielloDaria Maria Monti
Oct 28, 2019·The Journal of Pharmacology and Experimental Therapeutics·Cinzia Parolini
Feb 3, 2012·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Daria Maria MontiRenata Piccoli
Jan 20, 2020·The FEBS Journal·Placido IllianoCinzia Parolini
Jun 11, 2020·Cardiovascular Drugs and Therapy·Cinzia Parolini
Aug 26, 2020·The Journal of Clinical Endocrinology and Metabolism·Andrea DelbarbaAlberto Ferlin

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