Abstract
Alcohol misuse increases infections and cancer fatalities, but mechanisms underlying its toxicity are ill-defined. We show that alcohol treatment of human tracheobronchial epithelial cells leads to inactivation of giantin-mediated Golgi targeting of glycosylation enzymes. Loss of core 2 N-acetylglucosaminyltransferase 1, which uses only giantin for Golgi targeting, coupled with shifted targeting of other glycosylation enzymes to Golgi matrix protein 130-Golgi reassembly stacking protein 65, the site normally used by core 1 enzyme, results in loss of sialyl Lewis x and increase of sialyl Lewis a and α2-6sialo mucin O-glycans. The α2-6sialo mucin O-glycans induced by alcohol cause death of U937 macrophages mediated by sialic acid-binding immunoglobulin-like lectin 7. These results provide a mechanistic insight into the cause of the toxic effects of alcohol and might contribute to the development of therapies to alleviate its toxicity.