The Heme Oxygenase/Biliverdin Reductase System and Its Genetic Variants in Physiology and Diseases
Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced into bilirubin-IXα (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, cons...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-02-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/14/2/187 |
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| Summary: | Heme oxygenase (HO) metabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin-IXα (BV), the latter being reduced into bilirubin-IXα (BR) by the biliverdin reductase-A (BVR). Heme oxygenase exists as two isoforms, HO-1, inducible and involved in the cell stress response, and HO-2, constitutive and committed to the physiologic turnover of heme and in the intracellular oxygen sensing. Many studies have identified genetic variants of the <i>HO/BVR</i> system and suggested their connection in free radical-induced diseases. The most common genetic variants include (GT)n dinucleotide length polymorphisms and single nucleotide polymorphisms. Gain-of-function mutations in the <i>HO-1</i> and <i>HO-2</i> genes foster the ventilator response to hypoxia and reduce the risk of coronary heart disease and age-related macular degeneration but increase the risk of neonatal jaundice, sickle cell disease, and Parkinson’s disease. Conversely, loss-of-function mutations in the <i>HO-1</i> gene increase the risk of type 2 diabetes mellitus, chronic obstructive pulmonary disease, and some types of cancers. Regarding <i>BVR</i>, the reported loss-of-function mutations increase the risk of green jaundice. Unfortunately, the physiological role of the HO/BVR system does not allow for the hypothesis gene silencing/induction strategies, but knowledge of these mutations can certainly facilitate a medical approach that enables early diagnoses and tailored treatments. |
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| ISSN: | 2076-3921 |