Mechanism of alteration of poly(adenosine diphosphate-ribose) metabolism by hyperthermia.
The effects of hyperthermia on adenine nucleotide metabolism including NAD and poly(ADP-ribose) have been studied in confluent cultures of C3H10T1/2 cells. Cells replated immediately following hyperthermic treatment showed only 9% survival relative to controls while after a 24-h recovery period at 37 degrees C survival was 87% of control. Hyperthermic treatment caused no detectable effect on total cellular levels of either NAD or ATP but produced a prolonged increase in cellular content of poly(ADP-ribose). Studies of the mechanism of this effect show that a major alteration of poly(ADP-ribose) metabolism caused by hyperthermia involves a decrease in the rate of turnover of polymers of ADP-ribose. Normal polymer turnover rates were restored during recovery at 37 degrees C even in the presence of cyclohexamide. The results argue that poly(ADP-ribose) glycohydrolase activity is reversibly altered by hyperthermia. Inhibition of poly(ADP-ribose) synthesis following hyperthermia delays recovery of normal rates of protein synthesis and recovery of the ability of the cells to plate and form colonies.
Jonsson
G G
GG
Department of Biochemistry, Texas College of Osteopathic Medicine, University of North Texas, Fort Worth 76107.
Jacobson
E L
EL
Jacobson
M K
MK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D005334:Fever / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009243:NAD / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D009243:NAD; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; C037689:benzamide; D000255:Adenosine Triphosphate; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase