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Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase beta activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide.
Neuroscience. 2003; 119(4):1023-32.N

Abstract

Previous studies have shown that poly (ADP-ribose) polymerase (PARP) and DNA polymerase beta, nuclear enzymes, are associated with cell replication and DNA repair. The present study tests the hypothesis that hypoxia results in increased PARP and DNA polymerase activity in cerebral cortical neuronal nuclei to repair the hypoxia-induced damage to genomic DNA. Studies were conducted in 13 anesthetized and ventilated newborn piglets (age 3-5 days) divided into normoxic (n=5) and hypoxic (n=8) groups. Hypoxia was induced by decreasing inspired oxygen from 21% to 7% for 60 min. Cerebral tissue hypoxia was documented biochemically by determining the tissue levels of ATP and phosphocreatine (PCr). Following isolation of the cortical neuronal nuclei, the activity of PARP and DNA polymerase beta was determined. During hypoxia, the tissue ATP level decreased by 73% from 4.12+/-0.67 micromol/g brain to 1.12+/-0.34 micromol/g brain, and PCr decreased by 78% from 4.14+/-0.68-0.90+/-0.20 micromol/g brain. In hypoxic neuronal nuclei, PARP activity significantly increased from 5.88+/-0.51 pmol NAD/mg protein/h in normoxic nuclei to 10.04+/-2.02 (P=0.001). PARP activity inversely correlated with tissue ATP (r=0.78) and PCr levels (r=0.81). Administration of N-nitro-L-arginine prior to hypoxia decreased the hypoxia-induced increase in PARP activity by 67%. Endogenous DNA polymerase beta activity increased from 0.96+/-0.13 in normoxic nuclei to 1.39+/-0.18 nmol/mg protein/h in hypoxic nuclei (P<0.005). DNA polymerase beta activity in the presence of exogenous template increased from 1.54+/-0.14 in the normoxic to 2.42+/-0.26 nmol/mg protein/h in the hypoxic group (P<0.005). DNA polymerase beta activity in the presence or absence of template inversely correlated with the tissue ATP (r=0.95 and 0.84, respectively) and PCr levels (r=0.93 and 0.77, respectively). These results demonstrate that the activity of PARP and DNA polymerase beta enzymes increase with the increase in degree of cerebral tissue hypoxia. Furthermore, the results demonstrate a direct correlation between the PARP and the DNA polymerase beta activity. We conclude that tissue hypoxia results in increased PARP and DNA polymerase beta activities indicating activation of DNA repair mechanisms that may result in potential neuronal recovery following hypoxia and the hypoxia-induced increase in PARP activity is NO-mediated.

Authors+Show Affiliations

Department of Pediatrics, Room 701, 7th Floor Heritage Building, Neonatal Research Laboratory, Drexel University College of Medicine and St. Christopher's Hospital for Children, 3300 Henry Avenue, Philadelphia, PA 19129, USA. mishra@drexel.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12831861

Citation

Mishra, O P., et al. "Hypoxia-induced Modification of Poly (ADP-ribose) Polymerase and Dna Polymerase Beta Activity in Cerebral Cortical Nuclei of Newborn Piglets: Role of Nitric Oxide." Neuroscience, vol. 119, no. 4, 2003, pp. 1023-32.
Mishra OP, Akhter W, Ashraf QM, et al. Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase beta activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide. Neuroscience. 2003;119(4):1023-32.
Mishra, O. P., Akhter, W., Ashraf, Q. M., & Delivoria-Papadopoulos, M. (2003). Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase beta activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide. Neuroscience, 119(4), 1023-32.
Mishra OP, et al. Hypoxia-induced Modification of Poly (ADP-ribose) Polymerase and Dna Polymerase Beta Activity in Cerebral Cortical Nuclei of Newborn Piglets: Role of Nitric Oxide. Neuroscience. 2003;119(4):1023-32. PubMed PMID: 12831861.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypoxia-induced modification of poly (ADP-ribose) polymerase and dna polymerase beta activity in cerebral cortical nuclei of newborn piglets: role of nitric oxide. AU - Mishra,O P, AU - Akhter,W, AU - Ashraf,Q M, AU - Delivoria-Papadopoulos,M, PY - 2003/7/2/pubmed PY - 2003/9/6/medline PY - 2003/7/2/entrez SP - 1023 EP - 32 JF - Neuroscience JO - Neuroscience VL - 119 IS - 4 N2 - Previous studies have shown that poly (ADP-ribose) polymerase (PARP) and DNA polymerase beta, nuclear enzymes, are associated with cell replication and DNA repair. The present study tests the hypothesis that hypoxia results in increased PARP and DNA polymerase activity in cerebral cortical neuronal nuclei to repair the hypoxia-induced damage to genomic DNA. Studies were conducted in 13 anesthetized and ventilated newborn piglets (age 3-5 days) divided into normoxic (n=5) and hypoxic (n=8) groups. Hypoxia was induced by decreasing inspired oxygen from 21% to 7% for 60 min. Cerebral tissue hypoxia was documented biochemically by determining the tissue levels of ATP and phosphocreatine (PCr). Following isolation of the cortical neuronal nuclei, the activity of PARP and DNA polymerase beta was determined. During hypoxia, the tissue ATP level decreased by 73% from 4.12+/-0.67 micromol/g brain to 1.12+/-0.34 micromol/g brain, and PCr decreased by 78% from 4.14+/-0.68-0.90+/-0.20 micromol/g brain. In hypoxic neuronal nuclei, PARP activity significantly increased from 5.88+/-0.51 pmol NAD/mg protein/h in normoxic nuclei to 10.04+/-2.02 (P=0.001). PARP activity inversely correlated with tissue ATP (r=0.78) and PCr levels (r=0.81). Administration of N-nitro-L-arginine prior to hypoxia decreased the hypoxia-induced increase in PARP activity by 67%. Endogenous DNA polymerase beta activity increased from 0.96+/-0.13 in normoxic nuclei to 1.39+/-0.18 nmol/mg protein/h in hypoxic nuclei (P<0.005). DNA polymerase beta activity in the presence of exogenous template increased from 1.54+/-0.14 in the normoxic to 2.42+/-0.26 nmol/mg protein/h in the hypoxic group (P<0.005). DNA polymerase beta activity in the presence or absence of template inversely correlated with the tissue ATP (r=0.95 and 0.84, respectively) and PCr levels (r=0.93 and 0.77, respectively). These results demonstrate that the activity of PARP and DNA polymerase beta enzymes increase with the increase in degree of cerebral tissue hypoxia. Furthermore, the results demonstrate a direct correlation between the PARP and the DNA polymerase beta activity. We conclude that tissue hypoxia results in increased PARP and DNA polymerase beta activities indicating activation of DNA repair mechanisms that may result in potential neuronal recovery following hypoxia and the hypoxia-induced increase in PARP activity is NO-mediated. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/12831861/Hypoxia_induced_modification_of_poly__ADP_ribose__polymerase_and_dna_polymerase_beta_activity_in_cerebral_cortical_nuclei_of_newborn_piglets:_role_of_nitric_oxide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306452203001660 DB - PRIME DP - Unbound Medicine ER -