ß-cell Apoptosis: The Role of Apoptosis Repressor with CARD Domain (ARC) — ASN Events

ß-cell Apoptosis: The Role of Apoptosis Repressor with CARD Domain (ARC) (#30)

Steven Kahn 1
  1. VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA

Apoptosis repressor with CARD domain (ARC) is a potent inhibitor of apoptosis.  Its effect to decrease cell death is the result of its inhibition of the activity of a number of pro-apoptotic molecules in the extrinsic and intrinsic apoptosis pathways.  This anti-apoptotic function is exerted through molecular interactions with transducers of apoptosis at its CARD domain.  While ARC has been known to be present in cardiomyocytes, skeletal muscle cells and neurons, it is only recently that we and others have shown it is produced in beta cells. 

Islet amyloid formation is associated with an increase in beta-cell apoptosis, mediated in part through activation of a number of the proteins in the extrinsic and intrinsic pathways that are ARC targets.  Using adenoviruses, we have demonstrated that increasing ARC expression decreases beta-cell apoptosis, while decreasing its expression is associated with an increase in beta-cell apoptosis.  This effect of ARC to decrease beta-cell apoptosis is mediated in part by it binding to Bad and Bax, two molecules that are involved in mitochondrial activation.

The observed effects of ARC to decrease beta-cell apoptosis suggests that it may be a novel therapeutic to prevent the decrease in beta-cell mass observed in type 2 diabetes