Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells.

Chronic hypoxia inhibits rat thyroid function in vivo. To determine possible mechanisms, we studied the effect of hypoxia on iodide uptake, the involvement of second messengers, and cell membrane permeability in rat thyroid FRTL-5 cells. Since sublethal heat stress protects tissues from ischemia, we also determined effects of heat stress. The initial rate of iodide uptake in untreated cells was between 12.98 and 15.28 pmol/μg DNA/min. Hypoxia (5% O2) increased the rate of uptake in a time-dependent manner. Heating cells at 45°C for 15 min (heat shock) prior to exposure to hypoxia for 3 days inhibited the increase in the initial rate of I-uptake. Using fura-2, we found that the resting [Ca2+]i in suspended FRTL-5 cells was 65 ± 7 nM (n = 16). [Ca2+]i was not increased in cells exposed to hypoxia for 1 day, while a 3-day exposure increased [Ca2+]i by 43 ± 4% (p < 0.05); no additional increase occurred after 7 days of exposure. When cells were heated prior to hypoxia exposure for 3 days, the hypoxia-induced ...