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Zinc supplementation increases expression of transcription factors PU.1, KLF4, and Nrf2 in the lungs of alcohol‐fed rats
Author(s) -
Joshi Pratibha C,
Fan Xian,
Koval Michael,
Guidot David M
Publication year - 2013
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.27.1_supplement.640.5
Subject(s) - klf4 , zinc , transcription factor , alcohol , chemistry , endocrinology , bioavailability , medicine , in vivo , ethanol , in vitro , biology , biochemistry , pharmacology , gene , sox2 , microbiology and biotechnology , organic chemistry
Our group has previously shown in a rat model of alcohol ingestion that (1) cultured type II alveolar epithelial cells form a leaky barrier, (2) there is a decrease in transcription factors Nrf2 and KLF4 in these cells, (3) GM‐CSF signaling is dampened, and (4) either in vitro or in vivo zinc treatment increases tight junction proteins and tightens the epithelial barrier. In this study, we examined the expression of Nrf2, KLF4, and PU.1, a master transcription factor for GM‐CSF, by real time PCR in primary alveolar epithelial cells isolated from rats fed the Lieber‐DeCarli liquid diet with or without alcohol and alcohol plus zinc acetate (10, 100, 500 mg/L) for 8 weeks. Zinc supplementation of the alcohol diet significantly increased (p<.02) expression of PU.1, KLF4, and Nrf2 in a dose‐dependent manner as compared to the alcohol group and reached the control levels with 10, 100 and 500 mg/L zinc in the diet, respectively. The increase in Nrf2 expression by zinc treatment may explain why zinc is purported to have antioxidant properties whereas the higher expression of KLF4 may be due to its interaction with PU.1. In fact, KLF4 is a PU.1 target gene and we have shown before that zinc restores GM‐CSF signaling in the lungs of alcohol‐fed rats. Collectively, these data suggest a delicate interplay of transcription factors in the lungs of alcohol‐fed rats and their differential modulation by the bioavailability of zinc.