Pro-survival role of gelsolin in mouse beta-cells.
We have previously shown that the Ca(2+)-dependent actin-severing protein gelsolin plays an important role in regulated insulin secretion. The aim of this study was to determine the role of gelsolin in beta-cell survival as it has been shown to play a dual role in apoptosis in other cell types. MIN6 subclones B1 and C3, shown previously to express gelsolin at different levels (B1>>C3 cells), were used for this purpose. We demonstrate that B1 cells have lower levels of apoptosis and active caspase-3 when compared with C3 cells, in both standard (25 mmol/l glucose and 15% FCS) and deprived (5 mmol/l glucose and 1% FCS) conditions. Overexpression of gelsolin resulted in a decrease in the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)(+) and active caspase-3(+) cells. Conversely, knockdown of gelsolin by RNA interference in B1 cells caused an increase in the number of TUNEL(+) and active caspase-3(+) cells. Finally, the anti-apoptotic role of gelsolin was confirmed in purified primary mouse beta-cells where overexpression of gelsolin resulted in a decrease in the percentage of TUNEL(+) cells. In summary, our results show for the first time that gelsolin plays a pro-survival role in pancreatic beta-cells.
Yermen
Barbara
B
Department of Genetic Medicine and Development, University Medical Center, 1 rue Michel-Servet, 1211 Geneva-4, Switzerland. Barbara.Yermen@medecine.unige.ch
Tomas
Alejandra
A
Halban
Philippe A
PA
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D018260:Gelsolin / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D018260:Gelsolin; D034741:RNA, Small Interfering