Vitamin A depletion causes oxidative stress, mitochondrial dysfunction, and PARP-1-dependent energy deprivation Journal Article
| Authors: | Chiu, H. J.; Fischman, D. A.; Hammerling, U. |
| Article Title: | Vitamin A depletion causes oxidative stress, mitochondrial dysfunction, and PARP-1-dependent energy deprivation |
| Abstract: | A significant unresolved question is how vitamin A deprivation causes, and why retinoic acid fails to reverse, immunodeficiency. When depleted of vitamin A, T cells undergo programmed cell death (PCD), which is enhanced by the natural competitor of retinol, anhydroretinol. PCD does not happen by apoptosis, despite the occurrence of shared early events, including mitochondrial membrane depolarization, permeability transition pore opening, and cytochrome c release. It also lacks caspase-3 activation, chromatin condensation, and endonuclease-mediated DNA degradation, hallmarks of apoptosis. PCD following vitamin A deprivation exhibits increased production of reactive oxygen species (ROS), drastic reductions in ATP and NAD+ levels, and activation of poly-(ADP-ribose) polymerase (PARP) -1. These latter steps are causative because neutralizing ROS, imposing hypoxic conditions, or inhibiting PARP-1 by genetic or pharmacologic approaches prevents energy depletion and PCD. The data highlight a novel regulatory role of vitamin A in mitochondrial energy homeostasis. © FASEB. |
| Keywords: | nonhuman; t lymphocyte; animal cell; mouse; animals; mice; mice, knockout; animal tissue; cell death; apoptosis; animal experiment; caspase 3; enzyme activation; hypoxia; reactive oxygen species; reactive oxygen metabolite; cell hypoxia; oxidative stress; c57bl 6 mouse; adenosine triphosphate; endonuclease; retinol; homeostasis; mitochondria; lymphocytes; energy metabolism; mitochondrion; nad; leukemia cell line; jurkat cells; nicotinamide adenine dinucleotide; depletion; dna degradation; dna fragmentation; vitamin a; vitamin a deficiency; poly(adp-ribose) polymerases; disorders of mitochondrial functions; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; chromatin condensation; energy consumption; bioenergetics; vitamin a depletion |
| Journal Title: | FASEB Journal |
| Volume: | 22 |
| Issue: | 11 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2008-11-01 |
| Start Page: | 3878 |
| End Page: | 3887 |
| Language: | English |
| DOI: | 10.1096/fj.08-112375 |
| PUBMED: | 18676402 |
| PROVIDER: | scopus |
| PMCID: | PMC2574026 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 11" - "Export Date: 17 November 2011" - "CODEN: FAJOE" - "Source: Scopus" |
