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Cell death and autophagy under oxidative stress: roles of poly(ADP-Ribose) polymerases and Ca(2+)

Philippe Wyrsch1, Christian Blenn, Jessica Bader

  • 1Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland.

Molecular and Cellular Biology
|July 4, 2012
PubMed

Insights

Nuclear enzymes poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 regulate calcium (Ca2+) signaling, influencing cell death and autophagy. These enzymes control TRPM2 channels, impacting stress kinase pathways and cellular fate.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Oxidative stress triggers cellular responses like autophagy and cell death.
  • These processes are intrinsically linked to disruptions in calcium (Ca2+) signaling.
  • Nuclear enzymes poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 are implicated in cellular stress responses.

Purpose of the Study:

  • To elucidate the role of PARP1 and PARP2 in regulating Ca2+ signaling during oxidative stress.
  • To investigate the involvement of PARP1 and PARP2 in controlling autophagy and cell death pathways.
  • To identify the specific ion channels and kinase pathways regulated by PARP1 and PARP2.

Main Methods:

  • Investigated the impact of PARP1 and PARP2 on cytosolic Ca2+ shifts from extracellular and intracellular sources.
  • Analyzed the function of transient receptor potential melastatin 2 (TRPM2) channels in cellular and lysosomal membranes.
  • Examined stress kinase responses, including ERK1/2, AKT, p38, SAPK/JNK, CREB, and ATF-1 phosphorylation.

Main Results:

  • PARP1 and PARP2 were found to control Ca2+ fluxes associated with autophagy and cell death.
  • TRPM2 channels were identified as key mediators of these Ca2+ signals, influencing specific stress kinase pathways.
  • PARP1 acts as an autophagy suppressor post-oxidative stress, while cell death is linked to ERK1/2 and AKT activation.

Conclusions:

  • PARP1 and PARP2 play a critical role in the epigenetic regulation of autophagy and cell death.
  • The study highlights the intricate connection between PARP enzymes, Ca2+ signaling, TRPM2 channels, and stress kinase pathways in determining cellular fate.
  • These findings offer insights into the molecular mechanisms governing cell survival and death under oxidative stress conditions.

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