3, 5, 3'-Triiodothyronine determines the viability of gc cells after heat shock

The heat shock (HS) response is a characteristic disruption of protein synthesis which occurs in cells exposed to a variety of noxious stimuli. The effects of HS on thyroid hormone-responsive GC cells were studied in an attempt to devise an in vitro model for the adaptive changes in thyroid hormone action caused by nonthyroidal disease. HS enhanced GC cell synthesis of 70 K and 90 K proteins in a manner previously described as characteristic of the HS response in many tissues. A step-wise decrease in GC cell viability occurred when cells were exposed to 45 C for 10 to 35 min. HS (45 C, 20 min) resulted in a rapid decrease in binding of T₃ to nuclear receptors. Two hours after HS, analysis of T₃ binding to isolated nuclei showed a 50% fall in binding capacity (240 fmol/100 μg DNA) compared to non-HS control cells (540 fmol/100 μg DNA); no difference in dissociation constant (K_d) was observed. The effect of thyroid hormone on cell viability after HS was then determined. Thyroid hormone depletion (≪0.02 nM T₃) resulted in significantly (P ≪ 0.05) enhanced cell viability compared to cells cultured with physiological T₃ (0.2 nM) after incubation at 45 C for intervals of 10-35 min. This inverse relationship between medium T₃ content and cell tolerance of HS occurred over a wide range of T₃ concentrations. Mean cell viability after exposure to 45 C for 20 min was 44 ± 3% in T₃-depleted cultures (≪0.02 nM), 27 ± 1% to 32 ± 5% in cultures containing 0.07-0.5 nM T₃, and 13 ± 3% in cultures containing 5 nM T₃. Our results thus characterize the response to HS in GC cells and the relationship of this response to medium T₃. Similar to the effect of various nonthyroidal diseases on rat hepatocytes in vivo, HS resulted in a decrease in T₃ nuclear receptors. Similar to the adverse effect of thyroid hormone on morbidity in animals with experimental diseases or injury, GC cell viability after HS was inversely related to medium T₃ content. Thus the HS response in GC cells may be a valuable in vitro model relevant to the effect on thyroid hormone action caused by nonthyroidal disease.