1-O-Hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxy-∃-D-glucopyranosyl)-sn-glycerol (Gln) induces cell death with more autophagosomes which is autophagy-independent

Citations Over TimeTop 17% of 2009 papers

Abstract

Autophagic cell death has recently received a great deal of attention. However, a dependence of this type of cell death on the actual process of autophagy has only rarely been proven. Indeed, it is important to differentiate between cell death with an accumulation of autophagosomes and cell death actually caused by excessive or inhibited autophagy. The aim of this study was to elucidate the mechanism of action involved in the cytotoxicity of 1-O-hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxy-beta-D-glucopyranosyl)-sn-glycerol (Gln) and specifically the involvement of autophagy in the effects observed. Our results show that Gln induces cell death associated with large increases in autophagolysosome number and size. However the cell death is independent of autophagy and caspase activation. Instead, Gln leads to lysosomal membrane permeabilization with a resulting leakage of hydrolases into the cytosol, which are then directly involved in cell death. The increased number of autophagolysosomes, however, is just a side effect of the neutralization of the lysosomal pH by Gln.

Related Papers

• → Autophagy is a survival force via suppression of necrotic cell death(2012)78 cited
• → Chapter 2 Autophagic Cell Death(2009)55 cited
• Autophagy: Executor and Manager of Programmed Cell Death(2010)
• → Autophagy and Vacuole Formation(2017)2 cited
• → The Dual Roles for Autophagy in Cell Death and Survival(2006)