Inositol Lipid Turnover, Ca2+ Mobilization, and Increased Ca2+ Influx in Heat-Stressed Cells
We have investigated membrane permeability to Ca2+ and Ca2+ levels in cells subjected to heat stress. Heat caused a large and rapid rise in intracellular free calcium (Ca2+ i) within 2 min at 45°C Effects on transmembrane Ca2+ influx were more gradual, requiring 30 min at 45°C before increases were observed. The early rise in Ca2+ i appeared to be due to release from internal Ca2+ stores. Changes in Ca2+ homeostasis were correlated with alterations in membrane phosphoinositide (PI) turnover. The early rise in Ca2+ i was preceded by rapid (30 sec) release of inositol triphosphate, a PI catabolite that mobilizes Ca2+ from internal pools. Increased Ca2+ influx was closely correlated with membrane accumulation of phosphatidic acid, a lipid catabolite of PI with Ca2+ ionophoretic properties. The results indicate that heat, acting at the membrane, precipitates a cascade of interacting lipid and ionic changes that may be involved in the mediation of thermal injury.
KeywordsPC12 Cell Heat Stress Intracellular Free Calcium Early Rise Inositol Triphosphate
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