Loss of a calcium requirement for protein synthesis in pituitary cells following thermal or chemical stress

Ca2+ is required for the maintenance of high rates of translational initiation in GH3 pituitary cells (Chin, K.-V., Cade, C., Brostrom, C.O., Galuska, E.M., and Brostrom, M.A. (1987) J. Biol. Chem. 262, 16509-16514). Following thermal stress at 46 degrees C or chemical stress from exposure to sodium arsenite or 8-hydroxyquinoline, rates of amino acid incorporation in Ca2+-restored GH3 cells were reduced acutely to those of unstressed, Ca2+-depleted control preparations. Sodium arsenite treatment resulted in loss of ability to accumulate polysomes in response to Ca2+. Stressed cells allowed to recover for 2-8 h either with or without Ca2+ in the medium exhibited comparable, increasing rates of amino acid incorporation and the induction of heat shock proteins (hsp). Abolition of the Ca2+-dependent component of translation was proportional to the intensity of the stress. Mild thermal stress (41 degrees C) resulted in the induction of hsp 68 and the retention of Ca2+-dependent protein synthesis; hsp 68 was synthesized in a Ca2+-dependent manner. After arsenite stress, restoration of the Ca2+ requirement for protein synthesis occurred by 24 h, and was preceded by a transitional period during which polysomes accumulated in response to Ca2+ without concomitant increased rates of incorporation. Responses to stress are proposed to include an acute inhibition of normal protein synthesis involving the destruction of Ca2+-stimulated initiation and a protracted period of recovery involving synthesis of the hsp accompanied by Ca2+-independent amino acid incorporation and slowed peptide chain elongation.