Effect of hyperthermia (45 degrees C) on calcium flux in Chinese hamster ovary HA-1 fibroblasts and its potential role in cytotoxicity and heat resistance.
Hyperthermia caused a major increase in uptake of 45Ca2+ into Chinese hamster ovary HA-1 cells. Increased permeability to Ca2+ was observed with heating periods as brief as 45 degrees C for 4 min and reached a maximum at 45 degrees C for 30 min. In addition to elevation of Ca2+ influx, heat induced an increase in 45Ca2+ exchange with the extracellular Ca2+ pool. The effect of heat on Ca2+ permeability was transient, and Ca2+ influx returned to normal values by approximately 9 h at 37 degrees C. Comparison of the time courses of increased Ca2+ permeability and cell inactivation at 45 degrees C indicated that the heating time required for maximum permeability to Ca2+ was similar to the initial resistant "shoulder" period of the cell survival curve. This suggests that Ca2+ could play a permissive role in thermal cell inactivation; efficient cell killing may require a threshold concentration of intracellular Ca2+. The kinetics of heat-induced increase in Ca2+ permeability also resembled that for the induction of thermotolerance. This might suggest a messenger role for Ca2+ in thermotolerance induction. Direct increase in cellular Ca2+ levels with Ca2+ ionophore A23187 (5 X 10(-6) M) led to subsequent heat resistance. However, the heat resistance produced by A23187 was of a lesser magnitude than heat-induced thermotolerance. In addition, A23187 did not induce the stress protein species characteristic of thermotolerance (heat shock proteins), but instead led to the synthesis of a related set of proteins (glucose-regulated proteins). The data thus suggest a role for Ca2+ in the cellular effects of hyperthermia. They are also of potential clinical relevance in that cellular responses to heat might be modified pharmacologically, by the judicious use of Ca2+ active agents, such as Ca2+ ionophores and channel blockers.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D008715:Methionine / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D000001:Calcimycin; D008715:Methionine; D002118:Calcium