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Iron diminishes the in vitro biological effect of vanadium.
Ghio, Andy, J. Stonehuerner, J. Soukup, L. Dailey, M. Kesic, AND M. Cohen. Iron diminishes the in vitro biological effect of vanadium. Journal of Inorganic Biochemistry. Elsevier Science Ltd, New York, NY, 147:126-33, (2015).
Mechanistic pathways underlying inflammatory injury following exposures to vanadium-containing compounds are not defined. We tested the postulate that the in vitro biological effect of vanadium results from its impact on iron homeostasis. Human bronchial epithelial (HBE) cells exposed to vanadyl sulfate (VOS04) showed a time- and dose-dependent increase in vanadium relative to PBS. HBE cells exposed to VOS04 and then exposed to ferric ammonium citrate (FAC) significantly increased intracellular iron import supporting an interaction between the two metals. Following exposure to VOS04, there was an increase (336±73%) in RNA for divalent metal transporter 1 (DMT1), a major iron importer. With inclusion of VOS04 in the incubation, vanadium could be measured in the nuclear and mitochondrial fractions and the supernatant. Non-heme iron in the nuclear and mitochondrial fractions were decreased inmediately following VOS04 exposure while there was an increased concentration of non-heme iron in the supernatant. Provision of excess iron inhibited changes in the concentration of this metal provoked by VOS04 exposures. Using Amplex Red,VOS04 was shown to significantly increase oxidant generation by HBE cells in a time- and dose-dependent manner. HBE cells pre-treated with FAC and then exposed to VOS04 demonstrated a decreased generation of oxidants.Similarly, activation of the transcription factor NF-kB promoter and release of interleukin-6 and -8 were increased following VOS04 exposure and these effects were diminished by pre-treatment with FAC. We conclude that an initiating event in biological effect after exposure to vanadyl sulfate is a loss of requisite cell iron.
This research is designed to investigate the mechanistic pathways involved in vanadium induced inflammatory injury.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CLINICAL RESEARCH BRANCH