Hypoxemia induces expression of heme oxygenase-1 and heme oxygenase-2 proteins in the mouse myocardium.
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% O(2)). 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 sub-endocardial 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.
Han
Feng
F
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Japan.
Takeda
Kazuhisa
K
Ono
Masao
M
Date
Fumiko
F
Ishikawa
Kazunobu
K
Yokoyama
Satoru
S
Shinozawa
Yotaro
Y
Furuyama
Kazumichi
K
Shibahara
Shigeki
S
D000818:Animals; D006321:Heart; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009206:Myocardium / Q000201:enzymology*
D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2