Rapid degradation of poly(ADP-ribose) after injection into mouse bloodstream

  • Okajima Yasuhisa
    Division of Genome Stability Research, National Cancer Center Research Institute
  • Yoshida Tomoko
    ADP-ribosylation in Oncology Project, National Cancer Center Research Institute Kyoritsu University of Pharmacy Biochemistry Division, National Cancer Center Research Institute
  • Fujimori Hiroaki
    Division of Genome Stability Research, National Cancer Center Research Institute
  • Wang Junhui
    Division of Genome Stability Research, National Cancer Center Research Institute
  • Harada Hiromi
    Division of Genome Stability Research, National Cancer Center Research Institute
  • Suzuki Ylenia
    Biochemistry Division, National Cancer Center Research Institute Section of Biochemistry, Department of Life and Reproduction Sciences, University of Verona Strada Le Grazie
  • Suzuki Hisanori
    Section of Biochemistry, Department of Life and Reproduction Sciences, University of Verona Strada Le Grazie
  • Masutani Mitsuko
    Division of Genome Stability Research, National Cancer Center Research Institute Biochemistry Division, National Cancer Center Research Institute ADP-ribosylation in Oncology Project, National Cancer Center Research Institute

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  • Rapid Degradation of Poly(ADP-ribose) after Injection into the Mouse Bloodstream

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Extensive DNA damage leads to the activation of poly(ADP-ribose) polymerase and subsequently to the formation of poly(ADP-ribose). When the damage is severe or leads to cell death, poly(ADP-ribose) may leak into the blood circulation. The metabolism of poly(ADP-ribose) in the bloodstream is not well understood. Thus, in the present study, the metabolism of 32P-labeled poly(ADP-ribose) was followed in mice after injection of this labeled compound into the tail vein. The results showed that 5 min after injection more than half of the radioactivity was concentrated in acid-soluble fractions, namely in low molecular weight compounds in the blood, liver, and kidneys. Most of this radioactivity was in the form of inorganic phosphate, detected 5 min post-injection in the blood, kidneys, and urine. By contrast, the metabolites ADP-ribose and phosphoribosyl-AMP were not detected in any of the tissues nor in blood or urine. Taken together, these findings suggest that once poly(ADP-ribose) enters the bloodstream it is rapidly degraded, thereby preventing its accumulation in the blood.

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