Mechanism(s) of heat killing: accumulation of nascent polypeptides in the nucleus?
To investigate the possibility that nascent polypeptides released from polysomes by heat shock accumulate in the nucleus, cells were pulse labeled with [35S]methionine for two minutes and heated immediately thereafter at 45.5 degrees C for 10 minutes. When isolated nuclei were subjected to gel electrophoresis and subsequently autoradiographed, heated nuclei exhibited an approximately 10-fold increase in radioactive polypeptides in comparison to nonheated controls. These nascent polypeptides were nonspecific molecules covering a wide range of molecular weights. It is plausible that the accumulation of polypeptides in the nucleus results in hyperthermic cytotoxicity. Therefore, we propose that a potential target for heat killing is within the nucleus, at sites where nascent polypeptides accumulate after heat shock.
Lee
Y J
YJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073.
Borrelli
M J
MJ
Corry
P M
PM
D000818:Animals; D001345:Autoradiography; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006358:Hot Temperature; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D010053:Ovary; D011132:Polyribosomes / Q000187:drug effects; D011691:Puromycin / Q000494:pharmacology; D013462:Sulfur Radioisotopes
D006360:Heat-Shock Proteins; D013462:Sulfur Radioisotopes; D011691:Puromycin; D008715:Methionine