Science Inventory

CARBON MONOXIDE REVERSIBLY DISRUPTS IRON HOMEOSTATIS AND RESPIRATORY EPITHELIAL CELLS FUNCTION

Citation:

GHIO, A. J., J. STONEHUERNER, L. A. DAILEY, M. C. MADDEN, J. D. RICHARDS, Z. DENG, K. D. NGUYEN, F. YANG, AND C. A. PIANTADOSI. CARBON MONOXIDE REVERSIBLY DISRUPTS IRON HOMEOSTATIS AND RESPIRATORY EPITHELIAL CELLS FUNCTION. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 38(6):715-723, (2008).

Impact/Purpose:

research results

Description:

Iron dissociation from heme is a major factor in iron metabolism and cellular concentrations of the metal correlate inversely with the expression of heme oxygenase (HO). We tested the hypothesis that 1) exposure to a product of HO, carbon monoxide (CO), disturbs iron homeostasis in the lung and in cultured respiratory epithelial cells, 2) this disturbance includes both decreased uptake and increased release of cell metal, and 3) the effects of CO on cell homeostasis follow changes in metal homeostasis. We observed changes in iron levels in rats exposed to only 50 ppm CO for 24 hours. CO decreased non-heme iron concentrations in lung and increased those in liver. In respiratory epithelial cells cultured at air-liquid interface, CO exposure reversibly decreased cell non-heme iron and ferritin concentrations within 2 hours. Iron uptake by epithelial cells was significantly decreased despite increased expression of divalent metal transporter-1 while iron release was elevated. The loss of cell non-heme iron after CO reduced oxidative stress, blocked release of the pro-inflammatory mediator (interleukin-8), and interfered with cell proliferation. We conclude that CO affects cell iron content through both metal uptake and release mechanisms. This loss of cellular iron after CO causes certain biological effects of the gas that have been reported to be involved in the protection of cell viability.

URLs/Downloads:

AMERICAN JOURNAL OF RESPIRA CELL MOLECULAR BIOLOGY   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 06/01/2008
Record Last Revised: 04/06/2009
OMB Category: Other
Record ID: 166858