Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines. A possible strategy for the maintenance of intracellular heme level.

Abstract

Heme oxygenase consists of two structurally related isozymes, heme oxygenase-1 and and heme oxygenase-2, each of which cleaves heme to form biliverdin, iron and carbon monoxide. Expression of heme oxygenase-1 is increased or decreased depending on cellular microenvironments, whereas little is known about the regulation of heme oxygenase-2 expression. Here we show that hypoxia (1% oxygen) reduces the expression levels of heme oxygenase-2 mRNA and protein after 48 h of incubation in human cell lines, including Jurkat T-lymphocytes, YN-1 and K562 erythroleukemia, HeLa cervical cancer, and HepG2 hepatoma, as judged by northern blot and western blot analyses. In contrast, the expression level of heme oxygenase-1 mRNA varies under hypoxia, depending on the cell line; it was increased in YN-1 cells, decreased in HeLa and HepG2 cells, and remained undetectable in Jurkat and K562 cells. Moreover, heme oxygenase-1 protein was decreased in YN-1 cells under the conditions used, despite the induction of heme oxygenase-1 mRNA under hypoxia. The heme oxygenase activity was significantly decreased in YN-1, K562 and HepG2 cells after 48 h of hypoxia. To explore the mechanism for the hypoxia-mediated reduction of heme oxygenase-2 expression, we showed that hypoxia shortened the half-life of heme oxygenase-2 mRNA (from 12 h to 6 h) in YN-1 cells, without affecting the half-life of heme oxygenase-1 mRNA (9.5 h). Importantly, the heme contents were increased in YN-1, HepG2 and HeLa cells after 48 h of incubation under hypoxia. Thus, the reduced expression of heme oxygenase-2 may represent an important adaptation to hypoxia in certain cell types, which may contribute to the maintenance of the intracellular heme level.

• Authors: Yongzhao Zhang, Kazumichi Furuyama, Kiriko Kaneko, Yuanying Ding, Kazuhiro Ogawa, Miki Yoshizawa, Masaki Kawamura, Kazuhisa Takeda, Tadashi Yoshida, Shigeki Shibahara
• Journal: The FEBS journal (FEBS J) Vol. 273 Issue 14 Pg. 3136-47 (Jul 2006) ISSN: 1742-464X [Print] England
• PMID: 16787441 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• RNA, Messenger
• Heme
• Heme Oxygenase (Decyclizing)
• heme oxygenase-2

Topics

• Acclimatization (physiology)
• Carcinoma, Hepatocellular (enzymology, metabolism, pathology)
• Cell Hypoxia
• Cell Line
• Gene Expression Regulation, Enzymologic
• Half-Life
• HeLa Cells
• Heme (metabolism)
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Humans
• Isoenzymes (genetics, metabolism)
• Jurkat Cells
• K562 Cells
• Liver Neoplasms (enzymology, metabolism, pathology)
• RNA, Messenger (metabolism)
• T-Lymphocytes (enzymology, metabolism, pathology)
• Time Factors