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S‐adenosylmethionine(SAMe) improves the oxidative stressinduced lung epithelial barrier dysfunction in HIV‐1
Author(s) -
Fan Xian,
Raynor Robert,
Joshi Pratibha C,
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.914.7
Subject(s) - tight junction , intracellular , oxidative stress , glutathione , paracellular transport , barrier function , chemistry , microbiology and biotechnology , immunology , biology , permeability (electromagnetism) , biochemistry , membrane , enzyme
Lung disease is a major cause of death in people living with HIV. HIV viral proteins can directly induce epithelial dysfunction in the lung via mechanisms involving oxidative stresses such as glutathione (GSH) depletion. Because SAMe is a GSH precursor, we hypothesized that supplementation of SAMe would antagonize oxidative stress‐induced impairment of alveolar epithelial function in HIV‐1 transgenic (Tg) rats. Monolayers derived from alveolar epithelial cells (AEC) isolated from HIV‐1 Tg rats had markedly decreased intracellular GSH, abnormal tight junction (TJ) protein expression in the cell membranes, and increased permeability compared monolayers derived wild type rats. In contrast, treatment with SAMe in the culture medium restored intracellular GSH and improved the localization of TJ proteins in the cell membrane of HIV‐1 Tg monolayers. More importantly, SAMe attenuated the HIV‐1 viral protein‐induced AEC monolayer dysfunction as evidenced by both an increase in the transepithelial electrical resistance and a decrease in FITC‐dextran paracellular flux. Further, monolayers derived from HIV‐1 Tg rats whose diets had been supplemented with SAMe for 8 wks had significantly improved function compared to monolayers from untreated HIV‐1 Tg rats. Our findings raise the possibility that augmenting antioxidant defenses within the alveolar space could improve the lung health of HIV‐infected individuals.