# Vanadium in lung mitochondria oxidative stress

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $195,000

## Abstract

Summary
Title: Vanadium in lung mitochondria oxidative stress
Occupational exposure to vanadium (V) causes fibrotic lung injury, and circumstantial evidence suggests that
V from non-occupational exposures could also contribute to lung fibrosis. Experimental studies show that V
accumulates in mitochondria and causes oxidative stress, but the biology of V is poorly understood, especially
concerning dose-response effects on accumulation in lung and lung mitochondria and associated toxicologic
responses. Our preliminary data from patients with idiopathic pulmonary fibrosis (IPF) show that V is inversely
correlated with selenium (Se) in IPF lungs and lung mitochondria. Se protects against occupational levels of V
toxicity in rats, raising the possibility that if environmental V causes or potentiates fibrotic lung disease, then it
may be possible to develop strategies to decrease environmental V exposure or decrease risk by nutritional
intervention with Se. Thus, we propose a critical set of cell and animal experiments to define the dose-
response relationship of V with lung mitochondrial V, Se, oxidative stress, respiratory functions and profibrotic
signaling to test the plausibility that environmental V contributes to risk of lung fibrosis. Our first specific aim is
to determine the dose-response effects of V on Se-dependent antioxidant systems, metabolism and redox
signaling, in lung fibroblasts, a cell type relevant to lung fibrosis. Experiments will use ICP-MS to quantify
cellular loading of V and effects on Se contents. Seahorse technology will determine respiratory responses to
V. Fluorescent redox probes will measure mitochondrial H2O2 and superoxide production. An integrated
analysis of redox targets, metabolomics and transcriptomics will test for V disruption of energy metabolism and
mitochondrial signaling. Measures of cell proliferation, senescence and cell death will establish dose-response
characteristics of fibroblasts to V concentration range from very low, non-toxic to toxic exposure levels. Our
second specific aim is to determine the dose-response relationship of V with lung and lung mitochondrial
responses. Experiments will show whether in vivo administration of V to mice decreases lung and lung
mitochondrial content of Se and related mitochondrial activities. Experiments with two models of
administration will be performed, i.e., an acute intranasal vanadium pentoxide exposure at doses previously
shown to cause subsequent lung fibrosis and 4- and 20-month dose-response with V in drinking water to mimic
environmental exposure. Mouse lung tissue and isolated lung mitochondria will be analyzed for V and Se
contents to compare these with existing human lung and lung mitochondrial data. Functional assays will be
performed including mitochondrial Se-dependent enzymes, markers of profibrotic signaling and lung
histopathology. The results will have sustained impact by providing fundamental new information to link V
exposure dose to lung and ...

## Key facts

- **NIH application ID:** 9988718
- **Project number:** 1R21ES031824-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Young-Mi Go Kang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988718

## Citation

> US National Institutes of Health, RePORTER application 9988718, Vanadium in lung mitochondria oxidative stress (1R21ES031824-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9988718. Licensed CC0.

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