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Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission.
Proc Natl Acad Sci U S A. 2000 Feb 15; 97(4):1845-50.PN

Abstract

Poly(ADP-ribose) polymerase (PARP) transfers ADP ribose groups from NAD(+) to nuclear proteins after activation by DNA strand breaks. PARP overactivation by massive DNA damage causes cell death via NAD(+) and ATP depletion. Heretofore, PARP has been thought to be inactive under basal physiologic conditions. We now report high basal levels of PARP activity and DNA strand breaks in discrete neuronal populations of the brain, in ventricular ependymal and subependymal cells and in peripheral tissues. In some peripheral tissues, such as skeletal muscle, spleen, heart, and kidney, PARP activity is reduced only partially in mice with PARP-1 gene deletion (PARP-1(-/-)), implicating activity of alternative forms of PARP. Glutamate neurotransmission involving N-methyl-d-aspartate (NMDA) receptors and neuronal nitric oxide synthase (nNOS) activity in part mediates neuronal DNA strand breaks and PARP activity, which are diminished by NMDA antagonists and NOS inhibitors and also diminished in mice with targeted deletion of nNOS gene (nNOS(-/-)). An increase in NAD(+) levels after treatment with NMDA antagonists or NOS inhibitors, as well as in nNOS(-/-) mice, indicates that basal glutamate-PARP activity regulates neuronal energy dynamics.

Authors+Show Affiliations

Departments of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10677544

Citation

Pieper, A A., et al. "Poly(ADP-ribosyl)ation Basally Activated By DNA Strand Breaks Reflects Glutamate-nitric Oxide Neurotransmission." Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 4, 2000, pp. 1845-50.
Pieper AA, Blackshaw S, Clements EE, et al. Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. Proc Natl Acad Sci U S A. 2000;97(4):1845-50.
Pieper, A. A., Blackshaw, S., Clements, E. E., Brat, D. J., Krug, D. K., White, A. J., Pinto-Garcia, P., Favit, A., Conover, J. R., Snyder, S. H., & Verma, A. (2000). Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. Proceedings of the National Academy of Sciences of the United States of America, 97(4), 1845-50.
Pieper AA, et al. Poly(ADP-ribosyl)ation Basally Activated By DNA Strand Breaks Reflects Glutamate-nitric Oxide Neurotransmission. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1845-50. PubMed PMID: 10677544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission. AU - Pieper,A A, AU - Blackshaw,S, AU - Clements,E E, AU - Brat,D J, AU - Krug,D K, AU - White,A J, AU - Pinto-Garcia,P, AU - Favit,A, AU - Conover,J R, AU - Snyder,S H, AU - Verma,A, PY - 2000/3/4/pubmed PY - 2000/3/25/medline PY - 2000/3/4/entrez SP - 1845 EP - 50 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 97 IS - 4 N2 - Poly(ADP-ribose) polymerase (PARP) transfers ADP ribose groups from NAD(+) to nuclear proteins after activation by DNA strand breaks. PARP overactivation by massive DNA damage causes cell death via NAD(+) and ATP depletion. Heretofore, PARP has been thought to be inactive under basal physiologic conditions. We now report high basal levels of PARP activity and DNA strand breaks in discrete neuronal populations of the brain, in ventricular ependymal and subependymal cells and in peripheral tissues. In some peripheral tissues, such as skeletal muscle, spleen, heart, and kidney, PARP activity is reduced only partially in mice with PARP-1 gene deletion (PARP-1(-/-)), implicating activity of alternative forms of PARP. Glutamate neurotransmission involving N-methyl-d-aspartate (NMDA) receptors and neuronal nitric oxide synthase (nNOS) activity in part mediates neuronal DNA strand breaks and PARP activity, which are diminished by NMDA antagonists and NOS inhibitors and also diminished in mice with targeted deletion of nNOS gene (nNOS(-/-)). An increase in NAD(+) levels after treatment with NMDA antagonists or NOS inhibitors, as well as in nNOS(-/-) mice, indicates that basal glutamate-PARP activity regulates neuronal energy dynamics. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10677544/Poly_ADP_ribosyl_ation_basally_activated_by_DNA_strand_breaks_reflects_glutamate_nitric_oxide_neurotransmission_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10677544 DB - PRIME DP - Unbound Medicine ER -