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Iron chelation in PC12 cells alters the mRNA expression of monoamine‐related proteins
Author(s) -
Unger Erica Lynn,
Hao Lei,
Gonzalez Eduardo G,
Beard John L
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.694.9
Subject(s) - dopamine transporter , monoamine neurotransmitter , dopamine , transporter , biology , gene expression , signal transduction , downregulation and upregulation , microbiology and biotechnology , chemistry , gene , receptor , endocrinology , biochemistry , serotonin , dopaminergic
Iron deficiency in brain tissue induces a number of genomic alterations, some of which persist into adulthood despite iron repletion (Clardy et al 2006). To investigate potential transcriptional events underlying changes in neurochemistry and neurophysiology during acute iron deprivation, we used microarray gene analyses with follow‐up RT‐PCR to identify candidate pathways affected by iron chelation in PC12 cells. Desferrioxamine (200 mM) treatment for 24 hr resulted in 322 significantly upregulated and 313 downregulated genes. Slc6 (norepinephrine transporter) and Slc3 (anion transporters) families of genes were reduced more than 3 fold in iron‐chelated cells. RT PCR verified this and also showed 3‐fold decrease in dopamine transporter mRNA. A pathway oriented analysis showed genes involved in dopamine transporter trafficking and dopamine receptor signaling were significantly up‐ or down‐regulated including glycogen synthase kinase 3β, protein phosphatase 2B, ubiquitin 2c and regulator of G protein signaling 2. Transcription factors related to neuron development (Nurr1, Nur77 and Phox2a) were also affected. These studies indicate acute iron deprivation alters the gene expression of key proteins involved in the biology of monoamines and will allow us to begin to target key molecular pathways underlying iron deficiency‐induced changes in behavior and neurophysiology.