Nuclear membrane proteins in failing human dilated cardiomyopathy.

Abstract

Emerin (34 kDa) is a 254 amino acid protein located on the cytoplasmic surface of the inner nuclear membrane in cardiac muscle. It interacts with nuclear lamins and nuclear actin. Emerin is usually completely absent in Emery-Dreifuss muscular dystrophy, a condition that also manifests in the heart. Nuclear lamins are specialized nuclear proteins that line the inner nuclear membrane. Two isoforms, lamin A and C, differ in their C-terminal amino acids. Both are important in apoptosis and are degraded by caspase enzymes. Mutations in the rod domain of the lamin A/C gene are known to cause dilated cardiomyopathy (DCM) (Fatkin et al. New Engl. J. Med. 1999, 351, 1715-1724). We have used Western blots to detect emerin and lamin A/C in left ventricles from both nondiseased and failing DCM samples. The lamins form dimers, however it is not known if they are homodimers and / or heterodimers. In this report we compare and quantify expression levels of emerin from samples of left ventricles from ten failing DCM patients and five nondiseased (donor) hearts. We observed three lamin bands that suggest the expression of the three isoforms of the A-type lamin gene, lamin A, lamin C and lamin C2 (Ye et al. Subcellular Biochem. 1998, 31, 587-610). Preliminary data show that both lamin isoforms and emerin are present.