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Regulated expression of GRP78 during vasopressin‐induced hypertrophy of heart‐derived myocytes
Author(s) -
Brostrom Margaret A.,
Mourad Fadi,
Brostrom Charles O.
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1219
Subject(s) - vasopressin , endoplasmic reticulum , medicine , endocrinology , unfolded protein response , chaperone (clinical) , muscle hypertrophy , phorbol , hormone , protein biosynthesis , chemistry , biology , microbiology and biotechnology , signal transduction , biochemistry , protein kinase c , pathology
Although the development of cellular hypertrophy is widely believed to involve Ca 2+ signaling, potential supporting roles for sequestered Ca 2+ in this process have not been explored. H9c2 cardiomyocytes respond to arginine vasopressin with an initial mobilization of Ca 2+ stores and reduced rates of mRNA translation followed by repletion of Ca 2+ stores, up‐regulation of translation beyond initial rates, and the development of hypertrophy. Rates of synthesis of the endoplasmic reticulum (ER) chaperones, GRP78 and GRP94, were found to increase preferentially at early times of vasopressin treatment. Total GRP78 content increased 2‐ to 3‐fold within 8 h after which the chaperone was subject to post‐translational modification. Preferential synthesis of GRP78 and the increase in chaperone content both occurred at pM vasopressin concentrations and were abolished at supraphysiologic Ca 2+ concentrations. Co‐treatment with phorbol myristate acetate decreased vasopressin‐dependent Ca 2+ mobilization and slowed appearance of new GRP78 molecules in response to the hormone, whereas 24 h pretreatment with phorbol ester prolonged vasopressin‐dependent Ca 2+ mobilization and further increased rates of GRP78 synthesis in response to the hormone. Findings did not support a role for newly synthesized GRP78 in translational up‐regulation by vasopressin. However up‐regulation, which does not depend on Ca 2+ sequestration, appeared to expedite chaperone expression. This report provides the first evidence that a Ca 2+ ‐mobilizing hormone at physiologic concentrations signals increased expression of GRP78. Translational tolerance to depletion of ER Ca 2+ stores, typifying a robust ER stress response, did not accompany vasopressin‐induced hypertrophy. J. Cell. Biochem. 83: 204–217, 2001. © 2001 Wiley‐Liss, Inc.