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Role of Heme Catabolism in Neurodegenerative Diseases

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Heme Oxygenase in Biology and Medicine

Abstract

Heme oxygenase (HO), a microsomal enzyme that cleaves heme to produce biliverdin, ferric iron and carbon monoxide, is the rate-limiting step in heme degradation.1 To date, three HO isoforms (HO-1, HO-2 and HO-3) have been identified that catalyze this reaction. HO-1 is a 32kDa heat shock protein2 induced by numerous noxious stimuli,3 HO-2 is a constitutively synthesized 36kDa protein which is abundant in brain and testis,4 and HO-3 has structural homology with HO-2, but its ability to catalyze heme degradation is much less.5 Within the brain, the majority of HO activity is attributed to the HO-2 isozyme1 since the expression of HO-1 is normally very low in the brain and restricted to select neuronal and non-neuronal cell populations in the forebrain, diencephalons, cerebellum, and brain stem.1 However, in the brain, HO-1 increases markedly after heat shock, ischemia or glutathione depletion4,6,7 and, after heat shock or ischemia, increased HO-1 expression is shown in neuronal and glial cells throughout the brain.1,7,8 Therefore, HO-1 is known as an oxidative stress-inducible protein and plays a key role in heme catabolism, in which heme, a potential prooxidant, is converted to bilirubin, an antioxidant.9 However, HO-1 also produces other by-products, such as carbon monoxide, a signal transmitter, and free iron, another prooxidant. Thus, heme catabolism may be followed by a variety of metabolic processes and consequently whether HO-1 acts as an antioxidant or prooxidant seems to be highly dependent on environment.10

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Authors and Affiliations

  1. Department of Neurology, Tohoku University School of Medicine, Sendai, 980-8574, Japan

    Atsushi Takeda & Yasuto Itoyama

  2. Department of Neurology, Nishitaga National Hospital, Sendai, 982-8555, Japan

    Teiko Kimpara

  3. National Eye Institute, National Institutes of Health LRCMB-NEI, Bethesda, Maryland, 20892, USA

    R. Krishnan Kutty

  4. Department of Pharmacology, New York Medical College, Valhalla, New York, 10595, USA

    Nader G. Abraham

  5. VA Medical Center, Research Service (151), White River Junction, Vermont, 05009, USA

    Barney E. Dwyer

  6. Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, 44106, USA

    Robert B. Petersen, George Perry & Mark A. Smith

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  1. Atsushi Takeda
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Editors and Affiliations

  1. New York Medical College, Valhalla, New York, USA

    Nader G. Abraham

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Takeda, A. et al. (2002). Role of Heme Catabolism in Neurodegenerative Diseases. In: Abraham, N.G. (eds) Heme Oxygenase in Biology and Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0741-3_11

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  • DOI: https://doi.org/10.1007/978-1-4615-0741-3_11

  • Publisher Name: Springer, Boston, MA

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