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Roles of Zinc in Skeletal Muscle Cell Growth
Author(s) -
Zhang Xiangfeng,
Kutzler Louis,
Killefer John,
Novakofski Jan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a625-b
Subject(s) - cell growth , cyclin d1 , extracellular , zinc , mapk/erk pathway , intracellular , cell cycle , chemistry , cell , medicine , microbiology and biotechnology , endocrinology , signal transduction , biology , biochemistry , organic chemistry
Zinc deficiency, associated with reduced muscle growth, is a global problem, particularly among women and children in developing countries. The effect of extracellular zinc on IGF signaling was examined using DTPA, a non‐membrane permeable zinc chelator. Inhibition of IGF stimulated cell proliferation by DTPA was Zn 2+ specific because only Zn 2+ , and not other metals (Fe 2+ , Fe 3+ , Cr 2+ , Ca 2+ , La 3+ , Mg 2+ , Mn 2+ , Cu 2+ ) could restore IGF‐I stimulated cell proliferation, suggesting that zinc was necessary for IGF activity. Treatment with AG1024 (an inhibitor of IGF‐IR and insulin receptor) resulted in lower cell proliferation that was not further inhibited by DTPA treatment. Treatment with picropodophyllin (a specific IGF‐1R inhibitor) also resulted in lower cell proliferation, which was further inhibited by DTPA. Addition of Zn 2+ partially increased cell proliferation, suggesting that zinc was important for IGF signaling by both IGF‐R1 and the insulin receptor. However, Western blotting of MAPK and cyclin D1 indicated phosphorylation of MAPK and cyclin D1 were independent of DTPA or zinc for up to 6 hours of treatment. Cyclin D1 was decreased after 24 hours treatment with IGF‐I in the presence of DTPA, consistent with the effects of zinc depletion on cell proliferation. DTPA had only a small effect on intracellular zinc after 8 hours. Since elevation of MAPK and cyclin D1 for 6 hours would normally allow growth arrested cells to pass through G1 phase, these results suggest that inhibitory effects of extracellular zinc depletion on IGF mediated cell proliferation are either occurring via a convergent pathway or acting by a cell cycle inhibitor.