Nath K A
Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Kidney Int. 2006 Aug;70(3):432-43. doi: 10.1038/sj.ki.5001565. Epub 2006 Jun 14.
Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, converting heme to biliverdin, during which iron is released and carbon monoxide (CO) is emitted; biliverdin is subsequently converted to bilirubin by biliverdin reductase. At least two isozymes possess HO activity: HO-1 represents the isozyme induced by diverse stressors, including ischemia, nephrotoxins, cytokines, endotoxin, oxidants, and vasoactive substances; HO-2 is the constitutive, glucocorticoid-inducible isozyme. HO-1 is upregulated in the kidney in assorted conditions and diseases. Interest in HO is driven by the capacity of this system to protect the kidney against injury, a capacity likely reflecting, at least in part, the cytoprotective properties of its products: in relatively low concentrations, CO exerts vasorelaxant, antiapoptotic, and anti-inflammatory effects while bile pigments are antioxidant and anti-inflammatory metabolites. This article reviews the HO system and the extent to which it influences the function of the healthy kidney; it summarizes conditions and stimuli that elicit HO-1 in the kidney; and it explores the significance of renal expression of HO-1 as induced by ischemia, nephrotoxins, nephritides, transplantation, angiotensin II, and experimental diabetes. This review also points out the tissue specificity of the HO system, and the capacity of HO-1 to induce renal injury in certain settings. Studies of HO in other tissues are discussed insofar as they aid in elucidating the physiologic and pathophysiologic significance of the HO system in the kidney.
血红素加氧酶（HO）是血红素降解过程中的限速酶，可将血红素转化为胆绿素，在此过程中释放铁并释放一氧化碳（CO）；随后胆绿素由胆绿素还原酶转化为胆红素。至少有两种同工酶具有HO活性：HO-1代表由多种应激源诱导的同工酶，包括缺血、肾毒素、细胞因子、内毒素、氧化剂和血管活性物质；HO-2是组成型、糖皮质激素诱导型同工酶。HO-1在各种情况和疾病的肾脏中上调。对HO的关注源于该系统保护肾脏免受损伤的能力，这种能力可能至少部分反映了其产物的细胞保护特性：在相对较低的浓度下，CO具有血管舒张、抗凋亡和抗炎作用，而胆色素是抗氧化和抗炎代谢产物。本文综述了HO系统及其对健康肾脏功能的影响程度；总结了在肾脏中引发HO-1的情况和刺激因素；探讨了缺血、肾毒素、肾炎、移植、血管紧张素II和实验性糖尿病诱导的肾脏HO-1表达的意义。本综述还指出了HO系统的组织特异性，以及HO-1在某些情况下诱导肾损伤的能力。只要有助于阐明HO系统在肾脏中的生理和病理生理意义，就会讨论在其他组织中对HO的研究。
