| RRC ID |
42795
|
| Author |
Ding Y, Zhang YZ, Furuyama K, Ogawa K, Igarashi K, Shibahara S.
|
| Title |
Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines.
|
| Journal |
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.
|
| Volume |
273(23)
|
| Pages |
5333-46
|
| Published |
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
|
| Times Cited |
24
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
HMV-II(RCB0777) |
