RRC ID 42795
著者 Ding Y, Zhang YZ, Furuyama K, Ogawa K, Igarashi K, Shibahara S.
タイトル Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines.
ジャーナル FEBS J
Abstract Intracellular heme concentrations are maintained in part by heme degradation, which is catalyzed by heme oxygenase. Heme oxygenase consists of two structurally related isozymes, HO-1 and HO-2. Recent studies have identified HO-2 as a potential oxygen sensor. To gain further insights into the regulatory role of HO-2 in heme homeostasis, we analyzed the expression profiles of HO-2 and the biochemical consequences of HO-2 knockdown with specific short interfering RNA (siRNA) in human cells. Both HO-2 mRNA and protein are expressed in the eight human cancer cell lines examined, and HO-1 expression is detectable in five of the cell lines, including HeLa cervical cancer and HepG2 hepatoma. Down-regulation of HO-2 expression with siRNA against HO-2 (siHO-2) caused induction of HO-1 expression at both mRNA and protein levels in HeLa and HepG2 cells. In contrast, knockdown of HO-1 expression did not noticeably influence HO-2 expression. HO-2 knockdown prolonged the half-life of HO-1 mRNA twofold in HeLa cells. Transient transfection assays in HeLa cells revealed that the 4.5-kb human HO-1 gene promoter was activated with selective knockdown of HO-2 in a sequence-dependent manner. Moreover, HO-2 knockdown caused heme accumulation in HeLa and HepG2 cells only when exposed to exogenous hemin. HO-2 knockdown may mimic a certain physiological change that is important in the maintenance of cellular heme homeostasis. These results suggest that HO-2 may down-regulate the expression of HO-1, thereby directing the co-ordinated expression of HO-1 and HO-2.
巻・号 273(23)
ページ 5333-46
公開日 2006-12-1
DOI 10.1111/j.1742-4658.2006.05526.x
PII EJB5526
PMID 17064313
MeSH Down-Regulation* HeLa Cells Heme / metabolism Heme Oxygenase (Decyclizing) / genetics* Heme Oxygenase (Decyclizing) / metabolism Heme Oxygenase-1 / genetics* Heme Oxygenase-1 / metabolism Humans Jurkat Cells K562 Cells RNA, Messenger / metabolism RNA, Small Interfering Tumor Cells, Cultured
IF 4.392
引用数 24
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HMV-II(RCB0777)