Oxidative stress and mechanisms of cell death

  • “Basic research into the molecular nature of oxidative stress is being translated into the development of natural product based activators of Nrf-2 to combat the effects of photo-oxidative stress.”- Donna Zhang and Georg Wondrak.

  • Click here for more information on oxidative stress and mechanisms of cell death.

Relevance to SWEHSC: 

The unique exposure to UV radiation in the Southwest environment defines a population who would benefit greatly from chemopreventative measures, an objective embraced by NIEHS.

Cluster of Efforts: 

Investigators/Funding: Bowden (RFG3), Chen (RFG3), Jacobson E (RFG3), Jacobson M (RFG3), Lau (RFG3), Monks (RFG3), Romagnolo (RFG3), Smith (RFG3), Tsaprailis (Proteomics), Wondrak (RFG3), Zhang (RFG3): NIEHS/ES017473, NIEHS/ES015010, NIHLBI/HL076530, NIHLBI/HL089958, NIIDA/DA023525, NIGMS/GM070890, DOD/2009 BCRP, ACS/RSG-07-154-01-CNE, ABRC/ABRC0923

  • Genotoxic stress causes a specific upregulation of the message for ND1, a protein that regulates complex 1 of mitochondrial oxidative phosphorylation (Jacobson M). Additionally, ND1 upregulation can be regulated by the nuclear enzyme poly(ADP-ribose) polymerase via its effect on cellular NAD and ATP pools.
  • Cystatin C is released from cardiomyocytes, and can be used as a biomarker of oxidative injury in the myocardium (Chen).
  • All-trans-retinoic acid (aTRA) completely protects mice from renal ischemia/reperfusion (I/R) injury (Lau). Understanding retinoid mediated cytoprotection at the molecular and cellular level may provide insights into novel therapeutic strategies effective for clinical interventions during chemical induced tissue injury or hypoxia/ischemia-reperfusion injury.
  • In the majority of cases where PARP hyperactivation contributes to cell death, it promotes the translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus, causing DNA condensation and fragmentation, in an apparently caspase-independent fashion. However, Dr. Monks' group has recently shown that in HK-2 cells PARP-1 hyper-activation is not accompanied by the translocation of AIF from mitochondria to the nucleus, and that Ca2+ plays an important role in modulating PARP-dependent ROS-induced cell death.