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RAF and antioxidants prevent cell death induction after growth factor abrogation through regulation of Bcl-2 proteins

Katarzyna Koziel1, Julija Smigelskaite, Astrid Drasche

  • 1Daniel Swarovski Research Laboratory, Department of Visceral-, Transplant- and Thoracic Surgery, Innsbruck Medical University, Austria.

Experimental Cell Research
|August 13, 2013
PubMed

Insights

Survival signaling pathways and antioxidants protect cells from death by targeting Bcl-2 family proteins. This convergence point influences cell life and death decisions following growth factor withdrawal.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial reactive oxygen species (ROS) production is critical for growth factor (GF) withdrawal-induced cell death.
  • Previously, activated RAF, AKT, Bcl-2, and antioxidants equally protected against ROS accumulation and cell death.

Purpose of the Study:

  • To investigate whether survival signaling and antioxidant protection converge on shared or distinct molecular targets.
  • To elucidate the roles of RAF and AKT in regulating Bcl-2 family proteins during GF deprivation.

Main Methods:

  • Utilized NIH 3T3 fibroblasts and 32D promyeloid cells.
  • Employed serum deprivation and IL-3 withdrawal to induce GF abrogation.
  • Assessed Mcl-1 and Bim expression, BAX activation, and mitochondrial translocation.

Main Results:

  • Activated RAF, but not AKT, prevented Mcl-1 decline and Bim increase following GF withdrawal.
  • Both RAF and AKT suppressed BAX activation and mitochondrial translocation.
  • Antioxidants prevented BAX activation and cell death in 32D cells but had minimal impact on Bim or Mcl-1 expression.

Conclusions:

  • Bcl-2 family proteins serve as a convergence point for RAF signaling and ROS in regulating cell survival and death.
  • RAF signaling plays a distinct role from AKT in regulating Mcl-1 and Bim levels during GF deprivation.
Keywords:
AntioxidantsApoptosisBcl-2 proteinsMitochondriaRAFReactive oxygen species (ROS)

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