A family of hsp60-related proteins in pancreatic beta cells of non-obese diabetic (NOD) mice

Abstract

Eukaryotic hsp60s are plastid-specific molecular chaperones implicated in the pathogenesis of many inflammatory and autoimmune diseases. We have used immunoelectron microscopy, immunoblotting and subcellular fractionation of islet cells to determine whether analogous proteins with related function are expressed in other cellular structures and whether such hsp60-related proteins could serve as antigenic targets in autoimmune diabetes. Using a panel of monoclonal and polyclonal antibodies to human and yeast hsp60s and immunoelectron microscopy, the hsp60 antibody cross-reactive proteins were detected in secretory granules, mitochondria, synaptic-like microvesicles and microtubules of mouse pancreatic beta cells. The expression of microtubule-associated hsp60 was induced by an infiltration of islets by mononuclear cells. This novel inducible-form of hsp60-related protein was recognized as an antigen by sera from diabetic mice. Subcellular fractionation of islets indicated that the molecular size of hsp60-related proteins included 66, 62, 58, 55, 52 and 38 kDa. These results demonstrate that the pancreatic beta cells express a family of hsp60-related proteins, with members differentially expressed in distinct cellular compartments. These proteins bearing hsp60 epitopes were antigenic targets for autoimmune responses in diabetic NOD mice.