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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access published online on February 4, 2009

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, doi:10.1093/gerona/gln056
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Differential Regulation of Hepatic Heme Oxygenase-1 Protein With Aging and Heat Stress

Steven A. Bloomer1, Hannah J. Zhang1, Kyle E. Brown2,3,4 and Kevin C. Kregel1,4

1 Department of Integrative Physiology, University of Iowa, Iowa City
2 Iowa City Veterans Administration Medical Center, Iowa City
3 Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City
4 Program in Free Radical and Radiation Biology, Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City

Address correspondence to Kevin C. Kregel, PhD, Department of Integrative Physiology, 532 FH, University of Iowa, Iowa City, IA 52242. Email: kevin-kregel{at}uiowa.edu


   Abstract

Increased expression of heme oxygenase-1 (HO-1) in response to physiological stress is considered to be a protective response, which may be altered with aging. In this study, HO-1 expression was assessed following heat stress by immunoblotting of liver homogenates and isolated hepatocytes from young (6 months) and old (24 months) Fischer 344 rats and by immunohistochemistry. Livers of old rats showed higher baseline levels of HO-1, which was predominately localized to Kupffer cells. After heat stress, young animals showed a greater relative increase in hepatic HO-1, part of which was caused by increased numbers of nonparenchymal cells that were immunoreactive to HO-1. Consistent with these data, HO-1 was significantly upregulated after hyperthermia in vitro only in hepatocytes from young rats. Hence, aging alters stress-induced expression of HO-1 in a cell-specific manner, which may contribute to the diminished stress tolerance observed in older organisms.

Keywords Oxidative stress; Kupffer cells; Inflammation; Hyperthermia

Received: August 14, 2008; Accepted: November 13, 2008


Decision Editor: Huber R. Warner, PhD


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