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 #
1Z01ES090079-08
Application #
6838593
Study Section
(EBP)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2003
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
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
Tliba, Omar; Cidlowski, John A; Amrani, Yassine (2006) CD38 expression is insensitive to steroid action in cells treated with tumor necrosis factor-alpha and interferon-gamma by a mechanism involving the up-regulation of the glucocorticoid receptor beta isoform. Mol Pharmacol 69:588-96
Lu, Nick Z; Cidlowski, John A (2006) Glucocorticoid receptor isoforms generate transcription specificity. Trends Cell Biol 16:301-7
Lewis-Tuffin, Laura J; Cidlowski, John A (2006) The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann N Y Acad Sci 1069:1-9

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