Down‐regulation of amphiphysin‐1 is responsible for reduced receptor‐mediated endocytosis in the senescent cells

Abstract

ABSTRACT Senescent cells have been generally characterized to have improper responsiveness to external stimuli and inefficient uptake of materials compared with presenescent cells, probably by down‐regulation of receptor‐mediated endocytosis. Using transferrin‐uptake assay and Western blot of endocytosis‐related proteins, we found that a significant decrease of amphiphysin‐1 is strongly related to the reduction of receptor‐mediated endocytosis in both human diploid fibroblasts of multipassages and hydrogen peroxide‐induced premature senescence. We reconfirmed the pivotal role of amphiphysin‐1 in senescence by showing that transfection of dominant negative amphiphysin‐1 reduces transferrin uptake in presenescent cells and that microinjection of wildtype amphiphysin‐1 into senescent cells restores the ability of the transferrin uptake nearly up to that of the presenescent cell. We conclude that the loss of endocytotic activity of senescent cells is directly related to the down‐regulation of amphiphysin‐1, and its functional restorability can be induced by simple microinjection of amphiphysin‐1 gene in the senescent cells.