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Manganese modulates genes involved in regulation of cell cycle
Author(s) -
Taka Equar,
Reams Renee R,
Heiman Ann S,
Soliman Karam,
DarlingReed Selina F
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.1231.6
Subject(s) - cell cycle , biology , microbiology and biotechnology , neurotoxicity , signal transduction , gene , gene expression , cell cycle checkpoint , apoptosis , cyclin d1 , chemistry , genetics , organic chemistry , toxicity
Manganese (Mn) is a neurotoxic metal. Excessive accumulation of Mn in the globus pallidus and striatum leads to decreased dopamine and cell death in the Parkinsonian‐like syndrome called manganism. Efforts to understand Mn neurotoxicity have focused on oxidative stress, apoptosis, and cell cycle; however, the molecular targets of Mn neurotoxicity remain unknown. Thus, we hypothesized that manganese causes neurotoxicity by modulating genes involved in regulating cell cycle. The hypothesis was tested using rat pheochromocytoma (PC12) cells which are a widely accepted model for neuronal studies. Using microarray gene expression profiling and GeneSifter data analysis, we identified 223 genes whose expression level was altered by >1.5 or < −1.5–fold. Of these genes, 146 were up‐regulated while 77 were down‐regulated. Gene modulation was noted in several categories including: cellular processes (99 genes), metabolism (71 genes), development (45 genes), signal transduction (22 genes), and apoptosis (16 genes). Using Real‐time PCR, mRNA expression was confirmed for cyclin G1, c‐Jun, Jun‐B, Jun‐D and cdk4 known to be involved in cell cycle progression. Flow cytometry showed that Mn caused S‐phase cell cycle arrest. In conclusion, our findings uncovered the effects of Mn on genes involved in cell cycle, metabolism, development, signal transduction and apoptosis in PC12 cells. Supported by ATSDR and MBRS.