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SIRT2 mediates oxidative stress-induced apoptosis of differentiated PC12 cells

Hui Nie1, Yunyi Hong1, Xiaofei Lu1

  • 1Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University.

Neuroreport
|June 13, 2014
PubMed

Insights

Sirtuin 2 (SIRT2) promotes cell death from oxidative stress. Inhibiting SIRT2 or reducing its levels decreases apoptosis by lowering reactive oxygen species and caspase-3 activation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Sirtuin 2 (SIRT2) is implicated in neurodegenerative disease cell death.
  • Its specific role in oxidative stress-induced apoptosis remains largely unknown.

Purpose of the Study:

  • To investigate the function of SIRT2 in oxidative stress-induced cell death.
  • To elucidate the molecular mechanisms underlying SIRT2's involvement.

Main Methods:

  • Utilized differentiated PC12 cells as a model system.
  • Examined the effects of hydrogen peroxide (H2O2) exposure.
  • Employed SIRT2 gene silencing and a specific SIRT2 inhibitor (AGK2).
  • Assessed apoptosis, caspase-3 activation, and reactive oxygen species (ROS) levels.

Main Results:

  • H2O2 treatment significantly upregulated SIRT2 expression in PC12 cells.
  • SIRT2 silencing and AGK2 treatment markedly reduced H2O2-induced apoptosis.
  • These protective effects were associated with decreased caspase-3 activation.
  • SIRT2 silencing led to reduced ROS generation under oxidative stress conditions.

Conclusions:

  • SIRT2 plays a critical role in mediating cell death triggered by oxidative stress.
  • Targeting SIRT2 may offer a therapeutic strategy for conditions involving oxidative damage.

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