Cycloheximide increases the thermostability of proteins in Chinese hamster ovary cells.
Protein denaturation resulting from temperatures between 42.0 degrees C and 50 degrees C has been observed and implicated as the lethal lesion for hyperthermic cell killing. A logical corollary is that protection against hyperthermic killing requires stabilization of cellular proteins against thermal denaturation. To test this, Chinese hamster ovary cells were treated with the heat protector cycloheximide and then subjected to differential scanning calorimetry to measure protein denaturation. Cycloheximide stabilized proteins that denatured between 42 degrees C and 52 degrees C in control cells by increasing their transition (denaturation) temperature by an average of 1.3 degrees C. In addition, cycloheximide reduced the cytotoxicity of actinomycin D and adriamycin, suggesting that protein stabilization protects cells against stresses other than hyperthermia.
Borrelli
M J
MJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073.
Lee
Y J
YJ
Frey
H E
HE
Ofenstein
J P
JP
Lepock
J R
JR
D000818:Animals; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D007700:Kinetics; D010053:Ovary; D011489:Protein Denaturation / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*
D011506:Proteins; D003609:Dactinomycin; D004317:Doxorubicin; D003513:Cycloheximide