30 some years of heme oxygenase: from a "molecular wrecking ball" to a "mesmerizing" trigger of cellular events.

In the beginning, the microsomal HO system was presumed to be made of one isozymes, now known as HO-1, which was cytP450-dependent; and, was thought to be of physiological significance solely in the context of catalysis of hemoglobin heme to bile pigments and CO. A succession of discoveries including characterization of the system as an independent mono-oxygenase, identification of a second form, called HO-2, free radical quenching activity of bile pigments, analogous function of CO in cell signaling to NO, and characterization of the system as HSP32 cognates has led to such an impressive expansion in the number of reports dealing with the HO system that surpass anyone's expectation. This review is a compilation of certain older findings and recent events that together ensure placement of the HO system in the mainstream research for decades to come.

Thirty years of microbial P450 monooxygenase research: peroxo-heme intermediates--the central bus station in heme oxygenase catalysis.

Oxygen has always been recognized as an essential element of many life forms, initially through its role as a terminal electron acceptor for the energy-generating pathways of oxidative phosphorylation. In 1955, Hayaishi et al. [Mechanism of the pyrocatechase reaction, J. Am. Chem. Soc. 77 (1955) 5450-5451] presented the most important discovery that changed this simplistic view of how Nature uses atmospheric dioxygen. His discovery, the naming and mechanistic understanding of the first "oxygenase" enzyme, has provided a wonderful opportunity and scientific impetus for four decades of researchers. This volume provides an opportunity to recognize the breakthroughs of the "Hayaishi School." Notable have been the prolific contributions of Professor Ishimura et al. [Oxygen and life. Oxygenases, Oxidases and Lipid Mediators, International Congress Series, Elsevier, Amsterdam, 2002], a first-generation Hayaishi product, to characterization of the cytochrome P450 monooxygenases.

Heme oxygenase-1: from bench to bedside.

As aspects of basic science come to play an increasingly prominent role in clinical medicine, heme oxygenase-1 is one of several molecules emerging as a central player in diseases of the lung and intensive care unit. Although the apparent raison d'être of this enzyme is to dispose of heme, its activity results in cytoprotection against oxidative injury and cellular stresses. As the lung interfaces directly with an oxidizing environment, it is expected that heme oxygenase-1 would be involved in many aspects of lung health and disease. The protective effects of heme oxygenase-1 and products of its enzymatic activity, including carbon monoxide, biliverdin and bilirubin, and ferritin, have opened the door to potential therapeutic and disease-monitoring possibilities that one day may be applicable to pulmonary medicine. This article introduces readers to the history of heme oxygenase research, the role of this enzyme in the lung, and related new developments to look forward to in the fields of pulmonary and critical care medicine.