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Zinc deficiency impairs neuronal STAT1 and STAT3 nuclear translocation through oxidant‐mediated mechanisms.
Author(s) -
Aimo Lucila,
Mackenzie Gerardo G,
Oteiza Patricia I
Publication year - 2008
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.22.1_supplement.697.9
Subject(s) - cytoskeleton , microbiology and biotechnology , biology , stat1 , nuclear transport , cytochalasin d , chromosomal translocation , endocrinology , medicine , chemistry , signal transduction , cell nucleus , biochemistry , cytoplasm , cell , gene
Transcription factors STAT1 and 3 are involved in neuronal proliferation, survival and differentiation during development. Zinc (Zn) deficiency can lead to alterations in neonate and infant behavior, cognitive and motor performance that persist into adulthood. Therefore, we studied the effects Zn deficiency on STAT1 and 3, characterizing the role of oxidants and the cytoskeleton. The incubation of human neuroblastoma cells in Zn deficient media led to STAT1 and 3 activation that was inhibited by the antioxidant (±)‐α‐lipoic acid suggesting the involvement of oxidants in this process. However, a decrease in Zn levels led to an impaired transport of the active STAT1 and 3 from the cytosol into the nucleus. The relevance of the cytoskeleton for STAT nuclear transport was investigated. Vinblastine, colchicine or cytochalasin D impaired the nuclear transport of STAT1 and 3 indicating the need of a functional cytoskeleton. Similar data was obtained in E19 rat fetal brains, isolated from dams fed Zn deficient diets throughout gestation. Developmental Zn deficiency led to altered STAT1 and 3 nuclear translocations and a low in vitro fetal brain tubulin polymerization. Therefore, this study demonstrates the role of oxidants and the cytoskeleton in the modulation of STAT1 and 3, and the need of an adequate Zn status for their correct function in the nervous system. Supported by grants from UCDavis and NIH HD 01743.