Cholesterol depletion induces autophagy.

摘要: Autophagy is a mechanism to digest cells' own components, and its importance in many physiological pathological processes being recognized. But the molecular that regulates autophagy not understood detail. In present study, we found cholesterol depletion induces macroautophagy. The cellular human fibroblasts was depleted either acutely using 5mM methyl-beta-cyclodextrin or 10-20microg/ml nystatin for 1h, metabolically by 20microM mevastatin 200microM mevalonolactone along with 10% lipoprotein-deficient serum 2-3 days. By any of these protocols, marked increase LC3-II detected immunoblotting immunofluorescence microscopy, more extensive than caused amino acid starvation, i.e., incubation Hanks' solution several hours. induction autophagic vacuoles also observed other cell types, LC3-positive membranes were often seen as long tubules, >50microm length. suppressed phosphatidylinositol 3-kinase inhibitors accompanied dephosphorylation mammalian target rapamycin. electron induced indistinguishable from those after starvation. These results demonstrate decrease activates 3-kinase-dependent mechanism.