Heme oxygenases (HOs) are the enzymes responsible for the breakdown of heme and the generation of biliverdin/bilirubin and carbon monoxide (CO). The kidney is a complex organ consisting of many different cell types all working together for the single purpose of filtering the blood to eliminate waste products and conserving ions, minerals, and water necessary for life. HO enzymes and their products play a critical role in the normal function of the kidney as well as protecting the kidney from various insults including ischemia and exposure to nephrotoxins. For example, the HO metabolite, bilirubin, is a potent antioxidant which can limit damage to renal tubular epithelial cells following exposure to nephrotoxins associated with chemotherapy or traumatic injury. Another HO metabolite, CO, is an important vasodilator of renal blood vessels and helps protect against severe decreases in renal blood flow in conditions as diverse as exposure to radiocontrast agents and in hypertension-induced kidney disease. HO and its metabolites also play an important role in the survival of kidney cells after acute and chronic injuries by regulating important cell growth and programmed cell death pathways. The intent of this volume is to highlight the important role that HO enzymes and their related metabolites, bilirubin and CO, play in the regulation of renal function and in the response of the kidney to both acute and chronic pathologies. Table of Contents: Introduction to the HO System / HO and Renal Vascular Function / HO and Renal Tubule Function / HO and Acute Kidney Injury / HO and Chronic Kidney Injury / Future of Renal HO Research / References

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

his book provides a comprehensive summary of data from basic research on characterization, regulation, and function of heme oxygenase in mammalian systems. The book also includes a major section that covers the currently used clinical methods to suppress neonatal jaundice with emphasis on the newly developed use of synthetic metalloporophyrins. This book will be welcomed by researchers and students in pharmacology, biochemistry, pharmacy, neonatology, hematology, internal medicine, and endocrinology.

Heme oxygenase is an enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. Heme must be synthesised and degraded within an individual nucleated cell, as heme is essential for the maintenance of cellular homeostasis by sensing or using oxygen. Physiological heme degradation is catalysed by the two functional isozymes of heme oxygenase, heme oxygenase-1 (HO-1) and HO-2, yielding CO, iron, and biliverdin IX N. Heme oxygenase-1 (HO-1), has potent anti-inflammatory, anti-oxidant and anti-proliferative effects, is up-regulated by multiple stimuli and provides protection against oxidative stress. HO-1 also plays an important role in the regulation of cardiovascular function and is involved in many other diseases such as sickle cell disease. This new book brings together leading research from around the world in this field.