87 – Glucose-regulated Stress Proteins (GRPs) and Alcohol

This chapter discusses the interactions of Glucose-Regulated Stress Proteins (GRPs) and alcohol. The Endoplasmic Reticulum (ER) acts as the central hub for the protein-producing cellular machinery. Within this subcellular compartment processes—like protein folding, assembly and transport take place. Furthermore, a quality-control system, residing in the ER, is responsible for monitoring posttranslational tasks like N-linked glycosylation and out-sorting of misfolded proteins. The specific proteins responsible for the various functions are designated “chaperones;” among them the so-called “stress proteins.” Two of the lumenal stress proteins, glucose-regulated stress protein 78 kDa (GRP 78) and GRP 94, are intrinsic components of the folding and assembling unit within the majority of cell types. The GRPs are transcriptionally activated by stressors like glucose depletion of the cell, hypoxia and some noxious compounds like ethanol. One of the best-studied GRP-target protein interactions is the GRP 78-assisted μ-chain folding in the immunoglobulin-secreting B-cell. GRP 78 mRNA, a marker of ER-stress, was increased, indicating that the stress-induced response in GRP 78 expression was activated. Under ethanol-imposed cell stress, the assembling and quality-control tasks of the chaperones like GRP 78 are impaired.