The goal of this project is to define how basic cellular mechanisms suppress, activate and execute the process of apoptosis or programmed cell death. Apoptosis is a fundamental component of virtually all aspects of biology, being critical for both developmental and cellular homeostasis in all multi-cellular organisms. Extensive studies worldwide have now implicated either excess or impaired apoptosis in numerous human diseases including cancer, AIDS, autoimmune diseases, sepsis, as well as toxic responses to environmental agents. Additionally, many of the therapies used for the treatment of cancer work by the activation of inherent cellular apoptotic programs. A clear understanding of the cellular mechanisms involved in the control of apoptosis will have considerable impact on human health. Although an enormous literature describes agents that induce apoptosis and the signaling pathways that transduce these death signals, very little information exists on how different signals impinge on the common genetic pathway of apoptosis, particularly from a cell biological perspective.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES090079-13
Application #
7734504
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2008
Total Cost
$1,426,896
Indirect Cost
City
State
Country
United States
Zip Code
Muñoz-Llanos, Mauricio; García-Pérez, María A; Xu, Xiaojiang et al. (2018) MicroRNA Profiling and Bioinformatics Target Analysis in Dorsal Hippocampus of Chronically Stressed Rats: Relevance to Depression Pathophysiology. Front Mol Neurosci 11:251
Franco, Rodrigo; Bortner, Carl D; Schmitz, Ingo et al. (2014) Glutathione depletion regulates both extrinsic and intrinsic apoptotic signaling cascades independent from multidrug resistance protein 1. Apoptosis 19:117-34
Franco, Rodrigo; Cidlowski, John A (2012) Glutathione efflux and cell death. Antioxid Redox Signal 17:1694-713
Franco, R; Cidlowski, J A (2009) Apoptosis and glutathione: beyond an antioxidant. Cell Death Differ 16:1303-14
Scoltock, A B; Heimlich, G; Cidlowski, J A (2007) Glucocorticoids inhibit the apoptotic actions of UV-C but not Fas ligand in hepatoma cells: direct evidence for a critical role of Bcl-xL. Cell Death Differ 14:840-50
Franco, Rodrigo; Panayiotidis, Mihalis I; Cidlowski, John A (2007) Glutathione depletion is necessary for apoptosis in lymphoid cells independent of reactive oxygen species formation. J Biol Chem 282:30452-65
Bortner, Carl D; Cidlowski, John A (2007) Cell shrinkage and monovalent cation fluxes: role in apoptosis. Arch Biochem Biophys 462:176-88
Smoak, Kathleen; Cidlowski, John A (2006) Glucocorticoids regulate tristetraprolin synthesis and posttranscriptionally regulate tumor necrosis factor alpha inflammatory signaling. Mol Cell Biol 26:9126-35
Rhen, Turk; Cidlowski, John A (2006) Estrogens and glucocorticoids have opposing effects on the amount and latent activity of complement proteins in the rat uterus. Biol Reprod 74:265-74
Heimlich, Gerd; Cidlowski, John A (2006) Selective role of intracellular chloride in the regulation of the intrinsic but not extrinsic pathway of apoptosis in Jurkat T-cells. J Biol Chem 281:2232-41

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