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Journal of Biochemistry Advance Access published online on October 9, 2009
Journal of Biochemistry, doi:10.1093/jb/mvp153
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© The authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Hypoxemia Induces Expression of Heme Oxygenase-1 and Heme Oxygenase-2 Proteins in the Mouse Myocardium

Feng Hana,b,#, Kazuhisa Takedaa, Masao Onoc, Fumiko Datec, Kazunobu Ishikawad, Satoru Yokoyamaa, Yotaro Shinozawab, Kazumichi Furuyamaa and Shigeki Shibaharaa,*

aDepartment of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Japan, bDepartment of Emergency and Critical Care Medicine, Tohoku University School of Medicine, Japan, cDepartment of Pathology, Tohoku University Graduate School of Medicine, Japan, and dCenter for Medical Education and Career Development, Fukushima Medical University, Fukushima, Japan

*Corresponding author: Shigeki Shibahara Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan Tel: 81-22-717-8117; Fax: 81-22-717-8118. E-mail: shibahar{at}mail.tains.tohoku.ac.jp

Received August 28, 2009; Accepted September 9, 2009


  Abstract

Heme oxygenase (HO) catalyzes oxidative breakdown of heme, and constitutes two isozymes, HO-1 and HO-2. Here, we explored the tissue-specific regulation of expression of HO-1 and HO-2 under hypoxemia. There was no significant change in the overall expression levels of HO-1 and HO-2 mRNAs and proteins in the lung during adaptation of C57BL/6 mice to normobaric hypoxia (10% O2). However, immunohistochemical analysis revealed the increased expression of HO-1 and HO-2 proteins after 28 days of normobaric hypoxia in the pulmonary venous myocardium that is the extension of the left atrial myocardium into pulmonary venous walls. Moreover, the expression of HO-2 protein was increased in the subendocardial myocardium of ventricles under hypoxia, while HO-1 protein level was increased in the full-thickness walls. Thus, hypoxemia induces expression of both HO-1 and HO-2 proteins in the myocardium. Using C57BL/6 mice lacking HO-2 (HO-2-/-), which manifest chronic hypoxemia, we also showed that the HO-1 protein level in the lung was similar between HO-2-/- mice and wild-type mice. Unexpectedly, HO-1 protein level was lower by 35% in the HO-2-/- mouse liver than the wild-type liver. These results indicate that the expression of HO-1 protein is regulated in a tissue-specific manner under hypoxemia.

Key Words: bilirubin, heme oxygenase, heart, hypoxia, hypoxemia, liver, lung, myocardium, oxygen sensor

#Present address: Department of Anesthesiology, Beijing Jishuitan Hospital?31 Xinjiekou East Street, Xicheng District, Beijing 100035, China


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