Increased Expression of the Huntingtin Interacting Protein-1 Gene in Cells From Hutchinson Gilford Syndrome (Progeria) Patients and Aged Donors

Abstract

Hutchinson Gilford syndrome (progeria [PG]) is a human disease associated with accelerated aging. To elucidate the acceleration mechanism, we first tried to transform a PG-derived cell line by infection of a recombinant adenovirus expressing HPV (human papilloma virus)-E6 and HPV-E7 genes. The transfected PG cells had a greater number of population doublings (PD) (>80), faster doubling time, and less staining of senescence-associated β-galactosidase than the nontransfected PG cells. The transfected cells also showed markedly more detectable telomerase activity than the nontransformed cells. The expression levels of the genes in the E6-transduced and E7-transduced cell line were then compared with those of the nontransfected cell line using an mRNA differential display method, following reverse-transcriptase polymerase chain reaction analysis. Expression of huntingtin interacting protein-1 (HIP-1) gene was found to be increased not only in PG cells but also in fibroblast cells from aged healthy donors. Thus, HIP-1 might be a molecular assistant in the pathogenesis of the cellular senescent process in the human cells tested.