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Departments of Biochemistry and Medicine, Texas College of Osteopathic Medicine, University of North Texas, Fort Worth, Texas 76107 [G. G. J., E. L. J., M. K. J.]; and Centre de Recherche de l'Hotel-Dieu de Quebec, 11 Cote du Palais, Quebec, Quebec, Canada G1R 2J6 [L. M., G. G. P.]
The effects of supranormal temperature on the activity of poly(ADP-ribose) glycohydrolase were studied by assaying the enzyme in cell extracts derived from cells subjected to hyperthermia and comparing with extracts that were heated in vitro. The enzyme activity was reduced by both hyperthermic treatment of cells and by heating of cell extracts; however greater reductions were observed when intact cells were subjected to hyperthermia. The additional reduction observed when intact cells were heated was reversed when cells were allowed to recover at 37°C following hyperthermia. We postulate that hyperthermia alters poly(ADP-ribose) glycohydrolase activity by two mechanisms, an irreversible thermal denaturation of the enzyme and a reversible metabolic alteration. Changes in poly(ADP-ribose) glycohydrolase activity can account in full for the observed alterations of poly(ADP-ribose) metabolism that occur following hyperthermia.
1 This work was supported in part by grants from the NIH (CA43894); The Medical Research Council, Stockholm, Sweden; The Medical Faculty, University of Lund, Lund, Sweden; The Anna Cederbergs Foundation for Medical Research, Karolinska Institute, Stockholm, Sweden; The John and Augusta Persson's Foundation for Medical Research, Lund, Sweden; and The Medical Research Council of Canada and National Research Council of Canada.
2 Permanent address: Department of Molecular Ecogenetics, The Wallenberg Laboratory, University of Lund, P. O. Box 7031, 220 07 Lund, Sweden.
3 To whom requests for reprints should be addressed, at Department of Biochemistry, Texas College of Osteopathic Medicine, Fort Worth, TX 76107.
Received 11/ 9/87. Revised 2/22/88. Accepted 4/27/88.
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