TAILIEUCHUNG - Báo cáo khoa học: Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines

Intracellular heme concentrations are maintained in part by heme degrada-tion, 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 expres-sion profiles of HO-2 and the biochemical consequences of HO-2 knock-down with specific short interfering RNA (siRNA) in human cells. | ỊFEBS Journal Down-regulation of heme oxygenase-2 is associated with the increased expression of heme oxygenase-1 in human cell lines Yuanying Ding1 Yong Z. Zhang1 Kazumichi Furuyama1 Kazuhiro Ogawa2 Kazuhiko Igarashi3 and Shigeki Shibahara1 1 Department of Molecular Biology and Applied Physiology Tohoku University Schoolof Medicine Sendai Japan 2 Department of Molecular Pharmacology Tohoku University Schoolof Medicine Sendai Japan 3 Department of Biochemistry Tohoku University Graduate Schoolof Medicine Sendai Japan Keywords cancer cell lines heme homeostasis heme oxygenase isozymes short interfering RNA Correspondence S. Shibahara Department of Molecular Biology and Applied Physiology Tohoku University Schoolof Medicine 2-1 Seiryo-machi Aoba-ku Sendai Miyagi 980-8575 Japan Fax 81 22 717 8118 Tel 81 22 717 8117 E-mail shibahar@ Present address Department of Molecular Pharmacology Kanazawa University Graduate Schoolof MedicalScience 13-1 Takara-machi Kanazawa 920-8640 Japan Received 28 July 2006 revised 3 October 2006 accepted 4 October 2006 doi 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 .

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