mReg2 inhibits nuclear entry of apoptosis-inducing factor in mouse insulinoma cells

Abstract

We have reported earlier that murine-regenerating gene mReg2 protects MIN6 mouse insulinoma cells from ER stress and caspase-mediated apoptosis. In apoptotic cells, DNA damage is induced by the nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). Here we tested the hypothesis that mReg2 may regulate Scythe and/or hsp70 which influence the nuclear import of AIF. Treatment with thapsigargin (Tg) or doxorubicin induced an increase in nuclear AIF in MIN6 cells carrying the empty transfection vector (MIN6-VC) but not in cells overexpressing mReg2 (MIN6-mReg2). On one hand, nuclear Scythe was higher in the nucleus of MIN6-mReg2 compared with that in MIN6-VC cells. mReg2 did not alter the expression of AIF or Scythe. On the other hand, mReg2 induced the expression of hsp70 which is known to promote cytosolic retention of AIF. We conclude that mReg2 inhibits AIF-mediated apoptosis by promoting the nuclear presence of Scythe and inducing hsp70.

• AIF
• apoptosis
• hsp70
• mReg2
• MIN6 cells
• scythe

Declaration of interest

The authors report that they have no conflicts of interest. This work was supported by research grants from the Canadian Institutes of Health Research (MOP-84389) and Canadian Diabetes Association (OG-3-11-3469-JL). J. L. Liu is a senior Chercheurs-boursier of Fonds de la recherché en santé Quebec. L. Liu was a recipient of studentship support from the McGill Faculty of Medicine and the Research Institute and the Endocrine Division of McGill University Health Centre.