We have previously identified a deletion mutant of human apoB [apoB (Thr26_Tyr27del)] in a subject with primary hypobetalipoproteinemia. The present study determined the effect of Thr26_Tyr27del mutation on apoB secretion using transfected McA-RH7777 cells. Transient or stable transfection of apoB-48 containing the Thr26_Tyr27del mutation showed drastically reduced secretion of the mutant as compared to wild-type apoB- 48. No lipoproteins containing the mutant apoB-48 were secreted into the medium. Incubation of transfected cells in a lipid-rich medium in the presence of cycloheximide showed rapid turnover of cell-associated mutant apoB-48 as compared to that of wild-type apoB-48. Immunofluorescence experiments showed that the mutant apoB-48 was mostly localized in the endoplasmic reticulum. Treatment with the proteasomal inhibitor MG132 markedly attenuated the turnover of cell-associated mutant apoB-48, whereas treatment with inhibitors of autophagosomal/lysosomal function (e.g. 3-MA or ammonium chloride) had no effect. Taken together, these results indicated that the defective secretion of the Thr26_Tyr27delmutantwas associated with increased intracellular degradation of apoB through the proteasome-dependent pathway.

Characterization of a mutant form of human apolipoprotein B (Thr26_Tyr27del) associated with familial hypobetalipoproteinemia / Magnolo, A. Lucia; Noto, Davide; Cefalù, Angelo B; Averna, Maurizio; Calandra B., Sebastiano; Yao, Zemin; Tarugi, Patrizia Maria. - In: BIOCHIMICA ET BIOPHYSICA ACTA. - ISSN 0006-3002. - STAMPA. - 1861(2016), pp. 371-379.

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