|Yokoyama, Wallace - Wally|
Submitted to: Journal of Toxicology and Applied Pharmacology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/24/2007
Publication Date: 7/15/2007
Citation: Valacchi, G., Vasu, V.T., Yokoyama, W., Corbacho, A.M., Phung, A., Lim, Y., Aung, H.H., Cross, C.E., Davis, P.A. 2007. Lung Vitamin E Transport Processes are Affected by Both Age and Environmental Oxidants in Mice. Journal of Toxicology and Applied Pharmacology. 222(2):227-234. Interpretive Summary: Vitamin E levels in the plasma and lungs of mice exposed to oxidative stressors, ozone and cigarette smoke, were evaluated in young and old mice. The plasma Vitamin E levels were 25% in old mice but the Vitamin E levels in lungs were 15% lower. A novel finding was that the gene ATTP, Alpha tocopherol transport protein, was detected in lung tissue for the first time and was lower in lungs of adult mice. Ozone and cigarette smoke also caused reductions of ATTP in lung tissue. Vitamin E transport from the plasma to tissues by SRB1, scavenger receptor B1, was also lowered by oxidative stressors in aged mice. These findings indicate that age plays a role in Vitamin E levels and assessment of plasma levels may lead to erroneous conclusions.
Technical Abstract: Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies, the effects of age and two environmental oxidants ozone (O3) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m3 6 h/day) for four days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (pb0.05) and 15% lower (pb0.05) in plasma and lung tissue, respectively, in aged versus young mice, acute environmental exposure to O3 or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lungs showed lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O3 or CS induced declines in ATTP and SRB1 in both aged and young mice lungs. CD36 increased in both young and aged mice lungs upon exposure to O3 and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types.