AJP - Endocrinology and Metabolism, Vol 264, Issue 4 E519-E525, Copyright © 1993 by American Physiological Society
Role of cytosolic calcium in regulation of cytoskeletal gene expression by insulin
R. S. Weinstock, C. M. Saville and J. L. Messina
Department of Veterans Affairs Medical Center, Syracuse, New York.
Insulin and calcium ionophores rapidly stimulated transcription of the
cytoskeletal beta- and gamma-actin genes in serum-deprived rat H4-II-E
hepatoma cells. The calcium ionophore A23187 (1 microM) stimulated
transcription of the beta-actin gene by 7.3-, 5.4-, and 2.6-fold and the
gamma-actin gene by 5.9-, 5.6-, and 2.6-fold at 15, 30, and 60 min,
respectively. Ionomycin (1 microM) similarly increased beta- and
gamma-actin transcription. Insulin stimulated beta-actin transcription
11.4-fold and gamma-actin 8.4-fold at 30 min. alpha-Tubulin transcription
was induced by both insulin and calcium ionophores but to a lesser degree.
The effects of A23187 or ionomycin together with insulin for 30 min were no
greater than those of insulin alone. Insulin alone, however, did not
significantly increase measurable intracellular calcium concentrations in
fura-2-loaded cells. When cytosolic calcium was chelated using quin2
acetoxymethyl ester, the ability of A23187 to increase beta- and
gamma-actin transcription was completely abolished, whereas insulin's
ability to stimulate actin transcription was only partially inhibited. This
suggests that the regulation of gene transcription by insulin may include
calcium-dependent pathways but strongly implies that calcium-independent
pathways are also utilized.
