Heat shock decreases nuclear transport of 3,5,3'-triiodo-L-thyronine in clone 9 cells.
Thyroid hormone, T3, enters cells through an energy-dependent, saturable process and/or passive diffusion. Although the nucleus is the primary site of T3 action, exact mechanisms by which T3 is transported to nucleus are uncertain. In this report, initial cellular and nuclear uptake of T3 was determined using a rat liver cell line (clone 9), in which energy-dependent cellular T3 uptake was demonstrable. One to 5 mM sodium butyrate enhanced cellular T3 uptake with a concomitant increase in nuclear T3 uptake after 30 h. Increased cellular T3 uptake was associated with the increase in the maximum velocity of saturable cellular T3 uptake systems without affecting the Michaelis-Menten constant. Sodium butyrate, however, elicited a reduction in nuclear thyroid hormone receptor levels. On the other hand, heat shock (42 C for 60 min) reduced nuclear T3 uptake without affecting the Michaelis-Menten constant and maximum velocity of saturable cellular T3 uptake. Although nuclear receptor levels were reduced transiently after the heat shock, decreased nuclear T3 transport was not caused by the changes in the receptor levels. NADPH-dependent cytosolic T3 binding protein was undetectable in clone 9 cells before and after butyrate treatment or heat shock. In conclusion, sodium butyrate enhanced nuclear T3 uptake through the increase in cellular T3 uptake that is prerequisite to nuclear T3 transport. However, nuclear T3 uptake mechanisms independent of the cellular uptake system exist and are sensitive to heat shock. Nuclear receptors and cytosolic T3 binding proteins do not seem to be involved in the alteration of nuclear T3 uptake after sodium butyrate or heat shock. These findings suggest intracellular regulatory mechanisms of thyroid hormone transport.
Ichikawa
K
K
Department of Geriatrics, Shinshu University School of Medicine, Matsumoto-City, Japan.
Hashizume
K
K
Kobayashi
M
M
Nishii
Y
Y
Ohtsuka
H
H
Suzuki
S
S
Takeda
T
T
Yamada
T
T
D000818:Animals; D001692:Biological Transport; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002352:Carrier Proteins / Q000032:analysis; D002467:Cell Nucleus / Q000378:metabolism*; D002999:Clone Cells; D006358:Hot Temperature; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000032:analysis; D013963:Thyroid Hormones; D014284:Triiodothyronine / Q000493:pharmacokinetics*; D000097810:Thyroid Hormone-Binding Proteins
D002087:Butyrates; D020148:Butyric Acid; D002352:Carrier Proteins; D008565:Membrane Proteins; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D000097810:Thyroid Hormone-Binding Proteins