Biochemical pathways of apoptosis: nicotinamide adenine dinucleotide- deficient cells are resistant to tumor necrosis factor or ultraviolet light activation of the 24-kD apoptotic protease and DNA fragmentation

doi:10.1084/jem.183.2.463

This Article

	Full Text (PDF, 928K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wright, S. C.
	Articles by Larrick, J. W.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wright, S. C.
	Articles by Larrick, J. W.


Social Bookmarking

	What's this?

ARTICLES

Biochemical pathways of apoptosis: nicotinamide adenine dinucleotide- deficient cells are resistant to tumor necrosis factor or ultraviolet light activation of the 24-kD apoptotic protease and DNA fragmentation

SC Wright, QS Wei, DH Kinder and JW Larrick
Palo Alto Institute of Molecular Medicine, Mountain View, California 94043, USA.

The function of nicotinamide adenine dinucleotide (NAD) and adenosine diphosphate (ADP) ribosylation reactions in the mechanism of apoptotic cell death is controversial, although one theory postulates an essential role for NAD depletion by poly-ADP-ribose polymerase. The present study examined the role of intracellular NAD in tumor necrosis factor (TNF) and ultraviolet (UV) light-induced activation of the 24-kD apoptotic protease (AP24) leading to internucleosomal DNA fragmentation and death. Our results demonstrate that nutritional depletion of NAD to undetectable levels in two leukemia lines (U937 and HL-60) renders them completely resistant to apoptosis. This was attributed to a block in the activation of AP24 and subsequent DNA cleavage. Normal cells show an elevation of ADP-ribosyl transferase (ADPRT) in both the cytosol and nucleus after exposure to TNF, but before DNA fragmentation. ADPRT activity as well as cell death was suppressed by an inhibitor specific for mono-ADPRT. Nuclei from NAD-depleted cells were still sensitive to DNA fragmentation induced by exogenous AP24, indicating a selective function for NAD upstream of AP24 activation in the apoptotic pathway. We confirmed a requirement for intracellular NAD, activation of ADPRT, and subsequent NAD depletion during apoptosis in KG1a, YAC-1, and BW1547 leukemia cell lines. However, this mechanism is not universal, since BJAB and Jurkat leukemia cells underwent apoptosis normally, even in the absence of detectable intracellular NAD. We conclude that TNF or UV light-induced apoptotic cell death is not due to NAD depletion in some leukemia cell lines. Rather, NAD-dependent reactions which may involve mono-ADPRT, function in signal transduction leading to activation of AP24, with subsequent DNA fragmentation and cell death.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Watson, M., Roulston, A., Belec, L., Billot, X., Marcellus, R., Bedard, D., Bernier, C., Branchaud, S., Chan, H., Dairi, K., Gilbert, K., Goulet, D., Gratton, M.-O., Isakau, H., Jang, A., Khadir, A., Koch, E., Lavoie, M., Lawless, M., Nguyen, M., Paquette, D., Turcotte, E., Berger, A., Mitchell, M., Shore, G. C., Beauparlant, P. (2009). The Small Molecule GMX1778 Is a Potent Inhibitor of NAD+ Biosynthesis: Strategy for Enhanced Therapy in Nicotinic Acid Phosphoribosyltransferase 1-Deficient Tumors. Mol. Cell. Biol. 29: 5872-5888 [Abstract] [Full Text]
Yiasemides, E., Sivapirabu, G., Halliday, G. M., Park, J., Damian, D. L. (2009). Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 30: 101-105 [Abstract] [Full Text]
Devalaraja-Narashimha, K., Padanilam, B. J. (2009). PARP-1 Inhibits Glycolysis in Ischemic Kidneys. J. Am. Soc. Nephrol. 20: 95-103 [Abstract] [Full Text]
Jia, J., Wang, Y., Zhou, L., Jin, S. (2006). Expression of Pseudomonas aeruginosa Toxin ExoS Effectively Induces Apoptosis in Host Cells. Infect. Immun. 74: 6557-6570 [Abstract] [Full Text]
COLUSSI, C., ALBERTINI, M. C., COPPOLA, S., ROVIDATI, S., GALLI, F., GHIBELLI, L. (2000). H2O2-induced block of glycolysis as an active ADP-ribosylation reaction protecting cells from apoptosis. FASEB J. 14: 2266-2276 [Abstract] [Full Text]
Laouar, A., Glesne, D., Huberman, E. (1999). Involvement of Protein Kinase C-beta and Ceramide in Tumor Necrosis Factor-alpha -induced but Not Fas-induced Apoptosis of Human Myeloid Leukemia Cells. J. Biol. Chem. 274: 23526-23534 [Abstract] [Full Text]
Galande, S., Kohwi-Shigematsu, T. (1999). Poly(ADP-ribose) Polymerase and Ku Autoantigen Form a Complex and Synergistically Bind to Matrix Attachment Sequences. J. Biol. Chem. 274: 20521-20528 [Abstract] [Full Text]
Herceg, Z., Wang, Z.-Q. (1999). Failure of Poly(ADP-Ribose) Polymerase Cleavage by Caspases Leads to Induction of Necrosis and Enhanced Apoptosis. Mol. Cell. Biol. 19: 5124-5133 [Abstract] [Full Text]
Leveille, C., Zekki, H., Al-Daccak, R., Mourad, W. (1999). CD40- and HLA-DR-mediated cell death pathways share a lot of similarities but differ in their use of ADP-ribosyltransferase activities. Int Immunol 11: 719-730 [Abstract] [Full Text]
Ozawa, M., Ferenczi, K., Kikuchi, T., Cardinale, I., Austin, L. M., Coven, T. R., Burack, L. H., Krueger, J. G. (1999). 312-nanometer Ultraviolet B Light (Narrow-Band UVB) Induces Apoptosis of T Cells within Psoriatic Lesions. JEM 189: 711-718 [Abstract] [Full Text]
Hamasaki, A., Sendo, F., Nakayama, K., Ishida, N., Negishi, I., Nakayama, K.-i., Hatakeyama, S. (1998). Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the bcl-2-related A1 Gene. JEM 188: 1985-1992 [Abstract] [Full Text]
Caricchio, R., Reap, E. A., Cohen, P. L. (1998). Fas/Fas Ligand Interactions Are Involved in Ultraviolet-B-Induced Human Lymphocyte Apoptosis. J. Immunol. 161: 241-251 [Abstract] [Full Text]
Ghibelli, L., Fanelli, C., Rotilio, G., Lafavia, E., Coppola, S., Colussi, C., Civitareale, P., Ciriolo, M. R. (1998). Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB J. 12: 479-486 [Abstract] [Full Text]
Yamadori, I., Yoshino, T., Kondo, E., Cao, L., Akagi, T., Matsuo, Y., Minowada, J. (1998). Comparison of Two Methods of Staining Apoptotic Cells of Leukemia Cell Lines: Terminal Deoxynucleotidyl Transferase and DNA Polymerase I Reactions. J. Histochem. Cytochem. 46: 85-90 [Abstract] [Full Text]
Wright, S. C., Schellenberger, U., Wang, H., Kinder, D. H., Talhouk, J. W., Larrick, J. W. (1997). Activation of CPP32-like Proteases Is Not Sufficient to Trigger Apoptosis: Inhibition of Apoptosis by Agents that Suppress Activation of AP24, but Not CPP32-like Activity. JEM 186: 1107-1117 [Abstract] [Full Text]