Aging-associated increase of gelsolin for apoptosis resistance.
Gelsolin, a Ca(2+)-dependent actin regulatory protein, was recently suggested to participate in apoptosis regulation. In this study, we found that the level of gelsolin is elevated in senescent human diploid fibroblasts (HDFs) and also in the tissues of old rats, i.e., in the liver, kidney, heart, spleen, stomach, and brain, etc. The ubiquitous increase of gelsolin in the aged organs and cells led us to assume that it might be related with one of the cardinal senescent phenotypes, aging-associated apoptosis resistency. Thus, we tested the sensitivity of senescent cells to apoptosis by menadione, an apoptosis-inducing agent, before and after the down-regulation of gelsolin. The down-regulation of gelsolin in senescent HDFs, independently of Bcl-2 family expression, resulted in an increased sensitivity to menadione-induced apoptotic cell death. The observed ubiquitous increase of gelsolin in the senescent states of cells and tissues, and the increased sensitivity to apoptosis-induction by gelsolin down-regulation, suggests that gelsolin would be partly responsible for age-related apoptosis resistance.
Ahn
Jeong Soo
JS
Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul, South Korea.
Jang
Ik-Soon
IS
Kim
Duk-In
DI
Cho
Kyung A
KA
Park
Yong Hoon
YH
Kim
Kyungtae
K
Kwak
Chung Sil
CS
Chul Park
Sang
S
D000223:Adaptation, Psychological / Q000502:physiology; D000367:Age Factors; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018260:Gelsolin / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007928:Lethal Dose 50; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D024483:Vitamin K 3 / Q000494:pharmacology
D018260:Gelsolin; D016376:Oligonucleotides, Antisense; D024483:Vitamin K 3