Gene regulation of heme oxygenase-1 as a therapeutic target

被引：288
作者：
Immenschuh, S [1 ]
Ramadori, G [1 ]
机构：
[1] Univ Gottingen, Abt Gastroenterol & Endokrinol, Zentrum Innere Med, D-37075 Gottingen, Germany
来源：
BIOCHEMICAL PHARMACOLOGY | 2000年 / 60卷 / 08期
关键词：
cytoprotection; gene regulation; heme oxygenase-1; oxidative stress; redox signaling;
D O I：
10.1016/S0006-2952(00)00443-3
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation. HO regulates the cellular content of the pro-oxidant heme and produces catabolites with physiological functions. HO-1 is induced by a host of oxidative stress stimuli, and the activation of HO-1 gene expression is considered to be an adaptive cellular response to survive exposure to environmental stresses. Since overexpression of the HO-1 gene is also protective against the deleterious effects of experimental injuries, the specific induction of HO-1 by 'non-stressful' stimuli, eg. stimuli that are not associated with oxidative stress, such as adenosine 3',5'-cyclic monophosphate or cyclic guanosine 3',5'-monophosphate, may have important clinical implications. This review summarizes recent advances in the understanding of regulatory mechanisms of HO-1 gene expression, in particular the role of various redox-dependent and redox-independent signaling pathways. Models of experimental injuries are highlighted in which specific overexpression of the HO-1 gene either by targeted gene transfer or by pharmacological modulation has been demonstrated to provide therapeutic effects. BIOCHEM PHARMACOL 60;8:1121-1128, 2000. (C) 2000 Elsevier Science Inc.
引用
收藏
页码：1121 / 1128
页数：8
相关论文
共 86 条
[21]   The guanylate cyclase-coupled natriuretic peptide receptor: A new target for prevention of cold ischemia-reperfusion damage of the rat liver [J].
Gerbes, AL ;
Vollmar, AM ;
Kiemer, AK ;
Bilzer, M .
HEPATOLOGY, 1998, 28 (05) :1309-1317
[22]   Antibody-induced transplant arteriosclerosis is prevented by graft expression of anti-oxidant and anti-apoptotic genes [J].
Hancock, WW ;
Buelow, R ;
Sayegh, MH ;
Turka, LA .
NATURE MEDICINE, 1998, 4 (12) :1392-1396
[23]   PROTEIN-KINASES AND PHOSPHATASES - THE YIN AND YANG OF PROTEIN-PHOSPHORYLATION AND SIGNALING [J].
HUNTER, T .
CELL, 1995, 80 (02) :225-236
[24]   The rat heme oxygenase-1 gene is transcriptionally induced via the protein kinase a signaling pathway in rat hepatocyte cultures [J].
Immenschuh, S ;
Kietzmann, T ;
Hinke, V ;
Wiederhold, M ;
Katz, N ;
Muller-Eberhard, U .
MOLECULAR PHARMACOLOGY, 1998, 53 (03) :483-491
[25]   Nitric oxide mediates the lipopolysaccharide dependent upregulation of the heme oxygenase-1 gene expression in cultured rat Kupffer cells [J].
Immenschuh, S ;
Tan, M ;
Ramadori, G .
JOURNAL OF HEPATOLOGY, 1999, 30 (01) :61-69
[26]   Transcriptional induction of heme oxygenase-1 gene expression by okadaic acid in primary rat hepatocyte cultures [J].
Immenschuh, S ;
Hinke, V ;
Katz, N ;
Kietzmann, T .
MOLECULAR PHARMACOLOGY, 2000, 57 (03) :610-618
[27]   Transcriptional activation of the haem oxygenase-1 gene by cGMP via a cAMP response element activator protein-1 element in primary cultures of rat hepatocytes [J].
Immenschuh, S ;
Hinke, V ;
Ohlmann, A ;
Gifhorn-Katz, S ;
Katz, N ;
Jungermann, K ;
Kietzmann, T .
BIOCHEMICAL JOURNAL, 1998, 334 :141-146
[28]   Up-regulation of heme-binding protein 23 (HBP23) gene expression by lipopolysaccharide is mediated via a nitric oxide-dependent signaling pathway in rat Kupffer cells [J].
Immenschuh, S ;
Stritzke, J ;
Iwahara, S ;
Ramadori, G .
HEPATOLOGY, 1999, 30 (01) :118-127
[29]   Heme oxygenase-1 is regulated by angiotensin II in rat vascular smooth muscle cells [J].
Ishizaka, N ;
Griendling, KK .
HYPERTENSION, 1997, 29 (03) :790-795
[30]   Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain [J].
Itoh, K ;
Wakabayashi, N ;
Katoh, Y ;
Ishii, T ;
Igarashi, K ;
Engel, JD ;
Yamamoto, M .
GENES & DEVELOPMENT, 1999, 13 (01) :76-86
123456789