Heme Oxygenase 2 is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Heme oxygenase 2 (HMOX2, HO-2) is a constitutively expressed enzyme that catalyzes the degradation of heme into biliverdin, carbon monoxide, and free iron. Unlike its inducible counterpart HMOX1, HMOX2 provides basal heme degradation capacity and serves important neuroprotective functions in the central nervous system.
HMOX2 is a 316-amino acid protein with several key domains[1]:
HMOX2 degrades heme through a three-step reaction[2]:
The reaction produces three bioactive products:
HMOX2 is constitutively expressed, unlike HMOX1 which is stress-inducible[3]:
HMOX2 provides neuroprotection through multiple mechanisms[4]:
HMOX2 contributes to brain iron metabolism[5]:
In Parkinson's disease, HMOX2 alterations have been observed[6]:
HMOX2 plays a critical role after intracerebral hemorrhage[8]:
CO produced by HMOX2 acts as a gaseous neurotransmitter[9]:
CO signaling provides neuroprotection[10]:
| Protein | Interaction | Functional Outcome |
|---|---|---|
| HMOX1 | Complementary function | Inducible heme degradation |
| Ferritin | Iron storage | Sequesters released iron |
| Biliverdin reductase | Product conversion | Biliverdin to bilirubin |
| Nrf2 | Regulatory relationship | HMOX1 induction (not HMOX2) |
| Cytochrome P450 | Heme-dependent | Substrate for HMOX2 |
The HMOX2 gene is located on chromosome 16q13.3[11]:
HMOX2 polymorphisms have been associated with[12]:
CO-based therapeutics may complement HMOX2 function[13]:
Strategies to enhance HMOX2 activity[14]:
HMOX2-targeted therapy may complement iron chelation[15]:
Current research focuses on:
Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annual Review of Pharmacology and Toxicology. 1997. ↩︎
Ryter SW et al. Heme oxygenase-1 and -2: genetic analysis of their roles in cell stress defense. Antioxidants & Redox Signaling. 2002. ↩︎
Maines MD, Gibbs PE. 30 some years of heme oxygenase: from a "molecular wrecking ball" to a "mesmerizing" trigger of cellular events. Biochemical and Biophysical Research Communications. 2005. ↩︎
Schipper HM et al. Heme oxygenase-1 and neurodegeneration: expanding frontiers of a neuroprotective mechanism. Brain Research. 2009. ↩︎
Dang TN et al. Role of HMOX2 in brain iron homeostasis and neurodegeneration. Free Radical Biology and Medicine. 2011. ↩︎
Baranano DE, Snyder SH. Neural roles for heme oxygenase: contrasts to nitric oxide synthase. Proceedings of the National Academy of Sciences. 2001. ↩︎
Calabrese V et al. Heme oxygenase in Alzheimer's disease brain: implications for antioxidant strategies. Neurochemical Research. 2006. ↩︎
Wang J, Doré S. Heme oxygenase-2: a critical regulator of heme-mediated oxidative stress in the brain. Cellular and Molecular Biology. 2009. ↩︎
Maines MD. Carbon monoxide: an emerging regulator of cGMP in the brain. Molecular and Cellular Neuroscience. 2023. ↩︎
Queiroga CS et al. Carbon monoxide and the brain: beyond neurotransmission. Neurochemistry International. 2019. ↩︎
Maines MD et al. Heme oxygenase-2: characterization of the gene and its role in cellular stress defense. Journal of Biological Chemistry. 1994. ↩︎
Chen YH et al. Heme oxygenase-2 gene polymorphisms and risk of Parkinson's disease. Neuroscience Letters. 2012. ↩︎
Motterlini R, Foresti R. Heme oxygenase-1 as a target for drug discovery. Antioxidants & Redox Signaling. 2014. ↩︎
Duvigneau JC et al. Heme oxygenase-2: novel regulator of brain iron homeostasis. Brain Research. 2018. ↩︎
Nandar W, Connor JR. Ferroportin and iron regulation in neurodegeneration. Neurobiology of Disease. 2019. ↩︎