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

Lu Liu1, Subrata Chowdhury, Sadaf Uppal

  • 1Fraser Laboratories, Department of Medicine, McGill University Health Science Centre and Royal Victoria Hospital , Montreal, Quebec , Canada.

Growth Factors (Chur, Switzerland)
|November 6, 2014
PubMed

Insights

The murine-regenerating gene mReg2 prevents cell death by regulating apoptosis-inducing factor (AIF) nuclear import. It achieves this by increasing nuclear Scythe and inducing hsp70, thereby protecting MIN6 cells from ER stress.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Murine-regenerating gene mReg2 previously demonstrated protection of MIN6 mouse insulinoma cells against ER stress and apoptosis.
  • Apoptosis involves DNA damage induced by the nuclear translocation of mitochondrial apoptosis-inducing factor (AIF).

Purpose of the Study:

  • To investigate if mReg2 regulates Scythe and/or hsp70, proteins that influence the nuclear import of AIF.
  • To elucidate the mechanism by which mReg2 confers protection against apoptosis.

Main Methods:

  • MIN6 cells with and without mReg2 overexpression were treated with thapsigargin (Tg) or doxorubicin.
  • Nuclear AIF levels were assessed in treated cells.
  • Expression levels of AIF, Scythe, and hsp70 were analyzed.
  • Nuclear Scythe levels were quantified.

Main Results:

  • Treatment induced nuclear AIF in control cells (MIN6-VC) but not in mReg2-overexpressing cells (MIN6-mReg2).
  • Nuclear Scythe levels were elevated in MIN6-mReg2 cells compared to MIN6-VC cells.
  • mReg2 did not alter AIF or Scythe expression but induced hsp70 expression.
  • Hsp70 is known to promote the cytosolic retention of AIF.

Conclusions:

  • mReg2 inhibits AIF-mediated apoptosis.
  • mReg2 exerts its protective effect by promoting the nuclear presence of Scythe and inducing hsp70 expression.
  • These combined actions prevent the nuclear translocation of AIF, thus inhibiting apoptosis.
Keywords:
AIFMIN6 cellsapoptosishsp70mReg2scythe

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