Gelsolin for senescence-associated resistance to apoptosis

Abstract

One of the characteristics of the senescent cell is apoptotic resistance. Gelsolin, a Ca(2+)-dependent actin regulatory protein, is believed to regulate the intracellular movements which are necessary for cell growth, proliferation, and differentiation. Recently, gelsolin was suggested to play a role in apoptotic resistance, which led us to examine its involvement in the apoptotic resistance of senescent cells. We found that the protein and mRNA levels of gelsolin were increased in senescent human diploid fibroblasts (HDFs). Gelsolin was intracellularly co-localized to the actin stress fiber and distributed to the nucleus and mitochondria in old HDFs. To examine the anti-apoptotic function of gelsolin in senescent HDFs, we tried to downregulate the expression of gelsolin by using antisense oligonucleotide in old HDFs. We then treated the senescent HDFs with the apoptosis-inducing agent menadione. Downregulation of gelsolin in senescent HDFs resulted in increased sensitivity to menadione-induced apoptotic cell death. This suggests that gelsolin plays a role in the apoptotic resistance observed in senescent HDFs.