Heme Oxygenases: Cellular Multifunctional and Protective Molecules against UV-Induced Oxidative Stress

Ultraviolet (UV) irradiation can be considered as a double-edged sword: not only is it a crucial environmental factor that can cause skin-related disorders but it can also be used for phototherapy of skin diseases. Inducible heme oxygenase-1 (HO-1) in response to a variety of stimuli, including UV exposure, is vital to maintain cell homeostasis. Heme oxygenase-2 (HO-2), another member of the heme oxygenase family, is constitutively expressed. In this review, we discuss how heme oxygenase (HO), a vital rate-limiting enzyme, participates in heme catabolism and cytoprotection. Phylogenetic analysis showed that there may exist a functional differentiation between HO-1 and HO-2 during evolution. Furthermore, depending on functions in immunomodulation and antioxidation, HO-1 participates in disease progression, especially in pathogenesis of skin diseases, such as vitiligo and psoriasis. To further investigate the particular role of HO-1 in diseases, we summarized the profile of the HO enzyme system and its related signaling pathways, such as Nrf2 and endoplasmic reticulum crucial signaling, both known to regulate HO-1 expression. Furthermore, we report on a C-terminal truncation of HO-1, which is generally considered as a signal molecule. Also, a newly identified alternative splice isoform of HO-1 not only provides us a novel perspective on comprehensive HO-1 alternative splicing but also offers us a basis to clarify the relationship between HO-1 transcripts and oxidative diseases. To conclude, the HO system is not only involved in heme catabolism but also involved in biological processes related to the pathogenesis of certain diseases, even though the mechanism of disease progression still remains sketchy. Further understanding the role of the HO system and its relationship to UV is helpful for revealing the HO-related signaling networks and the pathogenesis of many diseases.

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The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073520 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3520

Author(s):

Ruka Nakasone ◽

Mariko Ashina ◽

Shinya Abe ◽

Kenji Tanimura ◽

Hans Van Rostenberghe ◽

...

Keyword(s):

Heme Oxygenase ◽

Immune Modulation ◽

Heme Oxygenase 1 ◽

Perinatal Complications ◽

Promoter Polymorphisms ◽

Functional Polymorphisms ◽

Published Evidence ◽

Definition Of ◽

Rate Limiting

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated.

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Protective role of heme oxygenase-1 in liver

Biologia ◽

10.2478/s11756-012-0058-1 ◽

2012 ◽

Vol 67 (4) ◽

Cited By ~ 3

Author(s):

Maher Abdalla ◽

Mary Mathahs ◽

Iman Ahmad

Keyword(s):

Oxidative Stress ◽

Heme Oxygenase ◽

Ferrous Iron ◽

Protective Role ◽

Heme Oxygenase 1 ◽

Multiple Forms ◽

Growing Body ◽

Rate Limiting ◽

Transcriptional Induction

AbstractHeme oxygenase-1 (HO-1) is the rate limiting enzyme in heme catabolism and degrades heme to carbon monoxide, biliverdin, and ferrous iron. HO-1 transcriptional induction occurs in response to multiple forms of chemical, physical stress and cytokines. HO-1 confers cytoprotection by inhibiting apoptosis, oxidative stress, and inflammation. Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. It has been shown that HO-1 induction and HO-1 products interfere with replication of HCV and markedly decreased HCV replication. However, a growing body of evidence indicates that induction of HO-1 may be involved in carcinogenesis and can play a role in the metastasis and growth of tumors. The antioxidant, antiviral activity of HO-1 makes it the cytoprotective enzyme for liver tissue in HCV infection, and induction of HO-1 can be suggested as a future therapeutic approach. However, the role of HO-1 in tumor growth should not be ignored.

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Heme Oxygenase-1 as a Pharmacological Target for Host-Directed Therapy to Limit Tuberculosis Associated Immunopathology

Antioxidants ◽

10.3390/antiox10020177 ◽

2021 ◽

Vol 10 (2) ◽

pp. 177

Author(s):

Krishna C. Chinta ◽

Hayden T. Pacl ◽

Anupam Agarwal ◽

Adrie J. C. Steyn

Keyword(s):

Disease Progression ◽

Heme Oxygenase ◽

Myeloid Cell ◽

Host Responses ◽

Heme Oxygenase 1 ◽

Cell Functions ◽

Promising Target ◽

Clinical Consequences ◽

Host Regulation

Excessive inflammation and tissue damage are pathological hallmarks of chronic pulmonary tuberculosis (TB). Despite decades of research, host regulation of these clinical consequences is poorly understood. A sustained effort has been made to understand the contribution of heme oxygenase-1 (HO-1) to this process. HO-1 is an essential cytoprotective enzyme in the host that controls inflammation and oxidative stress in many pathological conditions. While HO-1 levels are upregulated in animals and patients infected with Mycobacterium tuberculosis (Mtb), how it regulates host responses and disease pathology during TB remains unclear. This lack of clarity is due in part to contradictory studies arguing that HO-1 induction contributes to both host resistance as well as disease progression. In this review, we discuss these conflicting studies and the role of HO-1 in modulating myeloid cell functions during Mtb disease progression. We argue that HO-1 is a promising target for host-directed therapy to improve TB immunopathology.

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Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180717160623 ◽

2018 ◽

Vol 24 (20) ◽

pp. 2283-2302 ◽

Cited By ~ 9

Author(s):

Vivian B. Neis ◽

Priscila B. Rosa ◽

Morgana Moretti ◽

Ana Lucia S. Rodrigues

Keyword(s):

Neurodegenerative Diseases ◽

Heme Oxygenase ◽

Therapeutic Potential ◽

Redox Homeostasis ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Physiological Conditions ◽

And Oxidative Stress ◽

Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

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