Different faces of the heme-heme oxygenase system in inflammation

被引:466
作者
Wagener, FADTG
Volk, HD
Willis, D
Abraham, NG
Soares, MP
Adema, GJ
Figdor, CG
机构
[1] Univ Nijmegen, Dept Tumor Immunol, Med Ctr, NL-6500 HB Nijmegen, Netherlands
[2] Humboldt Univ, Dept Med Immunol, Charite, Berlin, Germany
[3] UCL, Dept Pharmacol, London, England
[4] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
[5] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Sch Med, Boston, MA 02215 USA
[6] Gulbenkian Inst Sci, Inflammat Lab, Lisbon, Portugal
关键词
D O I
10.1124/pr.55.3.5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The heme-heme oxygenase system has recently been recognized to possess important regulatory properties. It is tightly involved in both physiological as well as pathophysiological processes, such as cytoprotection, apoptosis, and inflammation. Heme functions as a double-edged sword. In moderate quantities and bound to protein, it forms an essential element for various biological processes, but when unleashed in large amounts, it can become toxic by mediating oxidative stress and inflammation. The effect of this free heme on the vascular system is determined by extracellular factors, such as hemoglobin/heme-binding proteins, haptoglobin, albumin, and hemopexin, and intracellular factors, including heme oxygenases and ferritin. Heme oxygenase (HO) enzyme activity results in the degradation of heme and the production of iron, carbon monoxide, and biliverdin. All these heme-degradation products are potentially toxic, but may also provide strong cytoprotection, depending on the generated amounts and the microenvironment. Pre-induction of HO activity has been demonstrated to ameliorate inflammation and mediate potent resistance to oxidative injury. A better understanding of the complex heme-heme oxygenase system may result in novel tools to combat diverse conditions, such as inflammation, atherosclerosis, transplant rejection, sickle cell disease, and cancer.
引用
收藏
页码:551 / 571
页数:21
相关论文
共 282 条
  • [11] Redox reactions of hemoglobin and myoglobin: Biological and toxicological implications
    Alayash, AI
    Patel, RP
    Cashon, RE
    [J]. ANTIOXIDANTS & REDOX SIGNALING, 2001, 3 (02) : 313 - 327
  • [12] Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury
    Amersi, F
    Buelow, R
    Kato, H
    Ke, BB
    Coito, AJ
    Shen, XD
    Zhao, DL
    Zaky, J
    Melinek, J
    Lassman, CR
    Kolls, JK
    Alam, J
    Ritter, T
    Volk, HD
    Farmer, DG
    Ghobrial, RM
    Busuttil, RW
    Kupiec-Weglinski, JW
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (11) : 1631 - 1639
  • [13] APPLEGATE LA, 1991, CANCER RES, V51, P974
  • [14] Modified hemoglobins produce venular interendothelial gaps and albumin leakage in the rat mesentery
    Baldwin, AL
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1999, 277 (02): : H650 - H659
  • [15] HEMIN - A POSSIBLE PHYSIOLOGICAL MEDIATOR OF LOW-DENSITY-LIPOPROTEIN OXIDATION AND ENDOTHELIAL INJURY
    BALLA, G
    JACOB, HS
    EATON, JW
    BELCHER, JD
    VERCELLOTTI, GM
    [J]. ARTERIOSCLEROSIS AND THROMBOSIS, 1991, 11 (06): : 1700 - 1711
  • [16] Ferriporphyrins and endothelium: a 2-edged sword - promotion of oxidation and induction of cytoprotectants
    Balla, J
    Balla, G
    Jeney, V
    Kakuk, G
    Jacob, HS
    Vercellotti, GM
    [J]. BLOOD, 2000, 95 (11) : 3442 - 3450
  • [17] ENDOTHELIAL-CELL HEME UPTAKE FROM HEME-PROTEINS - INDUCTION OF SENSITIZATION AND DESENSITIZATION TO OXIDANT DAMAGE
    BALLA, J
    JACOB, HS
    BALLA, G
    NATH, K
    EATON, JW
    VERCELLOTTI, GM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (20) : 9285 - 9289
  • [18] Neural roles for heme oxygenase:: Contrasts to nitric oxide synthase
    Barañano, DE
    Snyder, SH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (20) : 10996 - 11002
  • [19] A mammalian iron ATPase induced by iron
    Barañano, DE
    Wolosker, H
    Bae, BI
    Barrow, RK
    Snyder, SH
    Ferris, CD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (20) : 15166 - 15173
  • [20] Biliverdin reductase:: A major physiologic cytoprotectant
    Barañano, DE
    Rao, M
    Ferris, CD
    Snyder, SH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (25) : 16093 - 16098