The role of intracellular free calcium in the cellular response to hyperthermia

Abstract

The intracellular free calcium (Ca++i) concentration was measured in several cell lines after heating at 45.0 degrees C using flow cytometry with indo-1. Chinese hamster ovary 10B2 (CHO) cells do not stain well with indo-1, so a CHO mutant cell line (CHO IS1) isolated in our laboratory with much-improved stainability for indo-1 was used to study CA++i changes in heated CHO cells. BALB-3T3 (mouse) and EJ30 (human) cells were also studied. Cells were heated in the sample holder of the cell sorter in order to measure Ca++i within seconds after heating. Ca++i increased rapidly within the first 5 min of heating at 45.0 degrees C in all three lines, though the magnitude of the increase varied for each cell line. The Ca++i returned rapidly to baseline after heating in CHO IS1 cells and BALB-3T3 cells. After 5 min of heating, the Ca++i plateaued in the EJ30 and IS1 cells, but decreased in the 3T3 cells. There was an inverse relationship between the Ca++i after 10 min at 45 degrees C and survival for the different cell lines. Thermotolerant cells experienced a similar change in Ca++i during heating as non-thermotolerant cells, though the kinetics were somewhat different for the IS1 cells. A bimodal distribution of Ca++i developed in EJ30 cells by 2 min after heating. Cells sorted from the near-normal Ca++i region of the histogram had a 2-fold higher survival rate than the cells which had a high Ca++i concentration. These data support the view that Ca++i changes during heating are not the principal factor in heat-induced cell death.

Heat induced ‘masking’ of redox sensitive component(s) of the DNA-nuclear matrix anchoring complex

“…In the nuclei, the interaction between calreticulin and Erp57 is speculated to exert a regulatory effect 8 . Further calreticulin is known to respond to changes in calcium ion levels that are altered by heat shock 10 . Hsp60 is primarily a component of the mitochondria and finding it interacting with DNA is intriguing and warrants further investigation.…”

Acute temperature resistance threshold in heart mitochondria: Febrile temperature activates function but exceeding it collapses the membrane barrier

“…Supra-physiological hyperthermia (usually in the range of 42 -45 C) is clinically applied for cancer treatment [2,3]. However, it is still not clear why cells of different types of tumours display different temperature sensitivity [4,5], as well as why some normal types of cells are more sensitive (e.g. neurons, cardiomyocytes) than other normal cells [6][7][8][9].…”