The effect of gamma radiation and neocarzinostatin of NAD and ATP levels in mouse leukaemia cells

Goodwin, Patricia M.; Lewis, Paul; Davies, M. I.; Skidmore, Christopher J.; Shall, Sydney

doi:10.1016/0304-4165(78)90312-4

Cited by 102 publications

(54 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when cells were exposed to high doses of genotoxic agents, sustained activation of poly-ADP-ribosylation reactions, coinciding with an increase in the levels of poly-ADP-ribose polymers generated following DNA damage, was shown to rapidly decrease the half-life of NAD ϩ in a dose-dependent manner. In fact, intracellular NAD ϩ levels undergo a decrease to 10 to 20% of their normal levels within 5 to 15 min upon exposure of cells to very high doses of DNA-damaging agents (143,369 (339). In mammalian cells, 90% of free tryptophan is metabolized through the kynurenine pathway, leading to the de novo synthesis of NAD ϩ .…”

Section: Historical Overviewmentioning

confidence: 99%

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Hassa

Haenni

Elser

et al. 2006

Microbiol Mol Biol Rev

629

656

View full text Add to dashboard Cite

SUMMARY Since poly-ADP ribose was discovered over 40 years ago, there has been significant progress in research into the biology of mono- and poly-ADP-ribosylation reactions. During the last decade, it became clear that ADP-ribosylation reactions play important roles in a wide range of physiological and pathophysiological processes, including inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. ADP-ribosylation reactions are phylogenetically ancient and can be classified into four major groups: mono-ADP-ribosylation, poly-ADP-ribosylation, ADP-ribose cyclization, and formation of O-acetyl-ADP-ribose. In the human genome, more than 30 different genes coding for enzymes associated with distinct ADP-ribosylation activities have been identified. This review highlights the recent advances in the rapidly growing field of nuclear mono-ADP-ribosylation and poly-ADP-ribosylation reactions and the distinct ADP-ribosylating enzyme families involved in these processes, including the proposed family of novel poly-ADP-ribose polymerase-like mono-ADP-ribose transferases and the potential mono-ADP-ribosylation activities of the sirtuin family of NAD+-dependent histone deacetylases. A special focus is placed on the known roles of distinct mono- and poly-ADP-ribosylation reactions in physiological processes, such as mitosis, cellular differentiation and proliferation, telomere dynamics, and aging, as well as “programmed necrosis” (i.e., high-mobility-group protein B1 release) and apoptosis (i.e., apoptosis-inducing factor shuttling). The proposed molecular mechanisms involved in these processes, such as signaling, chromatin modification (i.e., “histone code”), and remodeling of chromatin structure (i.e., DNA damage response, transcriptional regulation, and insulator function), are described. A potential cross talk between nuclear ADP-ribosylation processes and other NAD+-dependent pathways is discussed.

show abstract

Section: Historical Overviewmentioning

confidence: 99%

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Hassa

Haenni

Elser

et al. 2006

Microbiol Mol Biol Rev

629

656

View full text Add to dashboard Cite

show abstract

“…Because the concentration of NAD + in cytoplasm or the nucleus of healthy cells is ≥70 μM, GAPDH binding in the nucleus may be inhibited under normal conditions as NAD + binding blocks the telomeric DNA binding to the Rossmann fold. Interestingly, it has been demonstrated that cellular stress depletes NAD + almost completely (41)(42)(43). Thus, the Rossmann fold on GAPDH may provide a cognate binding site for the telomeric DNA in a manner critically dependent on the elimination of NAD + from the Rossmann fold under stress conditions.…”

Section: Role Of the C-terminal Region Of Gapdh In Telomerase Inhibitmentioning

confidence: 99%

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

Nicholls

Pinto

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Oxidative stress regulates telomere homeostasis and cellular aging by unclear mechanisms. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key mediator of many oxidative stress responses, involving GAPDH nuclear translocation and induction of cell death. We report here that GAPDH interacts with the telomerase RNA component (TERC), inhibits telomerase activity, and induces telomere shortening and breast cancer cell senescence. The Rossmann fold containing NAD + binding region on GAPDH is responsible for the interaction with TERC, whereas a lysine residue in the GAPDH catalytic domain is required for inhibiting telomerase activity and disrupting telomere maintenance. Furthermore, the GAPDH substrate glyceraldehyde-3-phosphate (G3P) and the nitric oxide donor S-nitrosoglutathione (GSNO) both negatively regulate GAPDH inhibition of telomerase activity. Thus, we demonstrate that GAPDH is regulated to target the telomerase complex, resulting in an arrest of telomere maintenance and cancer cell proliferation. and apoptosis. Although production of daughter cells costs energy, it remains largely elusive how energy metabolism regulates normal cell aging and lifespan. Considerable evidence suggests that metabolic waste causes premature senescence and apoptosis, shortening cellular lifespan. Accumulation of reactive oxygen species (ROS) damages cellular enzymes, organelle membranes, and chromosomal DNA including telomeres (the ends of chromosomes) (1, 2). Whereas enzymes that reduce the production of metabolic hazards may operate to extend cellular lifespan, recent studies demonstrate that the energy producing enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that limits ROS production undergoes structural modifications and travel into the nucleus (3-7) to interact with telomeres directly and to potentially alleviate stress-induced cell aging (8, 9).Human telomeres are composed of arrays of a few thousand tandem DNA repeats of TTAGGG and various binding proteins. Telomeres undergo progressive shortening as somatic cells divide, due to the inability of cells to replicate the extreme ends of chromosomes. When telomeres are critically short, cells exit the cell cycle and undergo cell senescence (10-13). As a measure to maintain telomeres for continuous renewal of germ lines, development of embryonic stem cells, clonal expansion of lymphocytes, and immortalization of neoplastic cells, telomerase is activated to synthesize and maintain telomeres by reverse transcription (10-13).Telomerase is a large ribonucleoprotein complex containing the catalytic subunit telomerase reverse transcriptase (TERT) and an RNA template (reviewed in refs. 13 and 14). Human telomerase reverse transcriptase (hTERT) comprises 1,132 amino acid residues and human telomerase RNA (hTERC) is composed of 451 nucleotides (15-18). Reconstitution of telomerase activity in telomerase-negative cells can be achieved by expression of hTERT, demonstrating that hTERT is the rate-limiting component of the enzyme complex (19,20).GAPDH has long been recognize...

show abstract

“…As observed by others (Skidmore et al . 1979, Goodwin et al 1978), a supralethal X-ray dose was required to cause a significant drop in NAD content . This may indicate that at doses in the survival range the cellular regeneration of NAD is sufficient to provide substrate for ADPRT .…”

Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribose) Metabolism in Proliferating Versus Quiescent Cells and Its Relationship to Their Radiation Responses

Sweigert

Marston

Dethlefsen

1990

International Journal of Radiation Biology

View full text Add to dashboard Cite

The effect of gamma radiation and neocarzinostatin of NAD and ATP levels in mouse leukaemia cells

Cited by 102 publications

References 17 publications

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component

Poly(ADP-ribose) Metabolism in Proliferating Versus Quiescent Cells and Its Relationship to Their Radiation Responses

Contact Info

Product

Resources

About