An Investigation On Glucocorticoid Receptor Isoforms In Peripheral Blood Mononuclear Cells From Patients With Myasthenia Gravis

Backgrounds:Glucocorticoids (GC) are one of the most widely used anti-inflammatory drugs. The effects of GC are routinely exploited in treatment of many pathological conditions ranging from Myasthenia gravis (MG), asthma, rheumatoid arthritis, ulcerative colitis, multiple sclerosis (MS), and so on. However, the effects of GC differ from person to person. Moreover, prolonged GC treatment can result in GC resistance. Glucocorticoid resistance poses a challenging clinical problem in most autoimmune diseases and inflammatory diseases. Unfortunately, the molecular mechanisms underlying steroid unresponsiveness remain unknown. It is well known that the action is mediated through high affinity binding of GC to the glucocorticoid receptor (GR). It is necessary to explore the function of GR and its relations to GC efficacy.It is well known that alternative splicing of the human glucocorticoid receptor (hGR) primary transcript produces two highly homologous protein isoforms, termed hGRα and hGRβ, but it has been suggested that to act as a dominant-negative inhibitor of glucocorticoid action.An increasing number of studies in the latest few years have implicated that alternative splicing of the human glucocorticoid receptor (hGR) primary transcript produces two highly homologous protein isoforms, GRα and GRβ that differ only at their carboxy-termini. In the absence of ligand, GRα resides in the cytoplasm of cells in a multi-protein complex consisting two molecules of hsp90 and several additional proteins. The receptor undergoes a change in conformation upon hormone binding, resulting in the dissociation of hsp90 and other associated proteins. In its...