Heme Oxygenase


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In What Way Can Naturally Occurring Compounds Be Utilised To Up-Regulate Heme Oxygenase To Serve Protective Role In Various Inflammatory Conditions?


The central nervous system is responsible for causing a response to stimuli. Inflammation is a defensive response that is provided to an injury which has occurred over a tissue, ligament, etc. There can be different formations or reactions to these stimuli. Swelling, redness, generation of heat and pain are some of the formations that occur over the surface of the body (Choi and Alam, 1996). The response of the body towards external and internal injuries causes inflammation. There are different types of compounds that are helpful in protecting the body from such inflammations or inflammatory conditions (Gaedeke, Noble and Border, 2005). This assessment is based on a scientific study that aims to provide an understanding of the techniques which are responsible for the up-regulation of heme oxygenase.

The defence mechanism in the body takes the decisions and formulates the extraction of certain elements or compounds that are helpful in producing anti-inflammatory agents (Gong and et. al., 2013). The process through which heme oxygenase can be up-regulated has been depicted in this assessment.

Naturally Occurring Compounds

The defence mechanism is initiated by the central nervous system of the human body when certain types of injury or harm have been caused in the form of stimuli (Harju and et. al., 2002). The response that is given by the body is in the form of redness swelling or heating of the affected area. There are certain compounds which initiate this process. These include the movement of plasma, leukocytes, etc. The nature of inflammation can be acute or chronic depending on the type of injury caused to the patient (Kietzmann, Samoylenko and Immenschuh, 2003).

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Heme Oxygenase (HO)

An enzyme that is generated for speeding up the breaking down of heme is heme oxygenase (Kim and et. al., 2010). The breakdown process results in the production of biliverdin, ferrous iron and carbon monoxide. These are generated in conditions of metainflammation. HO is also referred to as a rate-limiting enzyme because it ends up in the production of iron and carbon monoxide. The inflammation condition is enhanced when this enzyme is generated. The central nervous system is responsible for the production of stress proteins when certain harmful stimuli have been addressed by the human body (Lang and et. al., 2005). HO is a system that acts like antioxidants. They are also responsible for regulating the vascular tone which enhances the protective responses.

The catalytic reaction that is responsible for breaking down iron and carbon monoxide aids inflammatory conditions. In order to prevent severe health conditions, the nervous system regulates the inflammations (Martin and et. al., 2004). HO is a catalyst in this breakdown process. Belonging to the stress protein family, the generation or occurrence of this compound takes place only when injuries or harmful stimuli are subjected towards the body. There are three isoforms of HO HO-1, HO-2 and HO-3. The compound is not only helpful in the production of iron and heme but also helpful in the regulation of various physiological and pathophysiological processes (Paine and et. al., 2010).

There are different conditions in which isoforms of HO are produced and found. The affected area is deformed or disoriented due to injury (Poss and Tonegawa, 1997). Cases of liver inflammation are regulated by the production of HO-1 and iron. The compound iron is degraded into iron and carbon monoxide with the help of heme oxygenase. This is further utilised in producing and regulating the inflammation conditions at the liver (Raju, McCoubrey and Maines, 1997). Being a crucial organ of the body, any damage caused to the liver can even result in the death of the person. Hence, this protective mechanism is initiated so that quick medical help or attention can be grabbed by the patient and certain solutions can be acquired.

Role of Heme Oxygenase in Protecting Inflammatory Conditions

There are various roles of HO when it comes to protection and inflammations. Apart from being an enzyme and catalyst in the breakdown process, this naturally occurring compound is responsible for the liberation of certain compounds that aid pathological and physiological processes (Xia and et. al., 2007). The physiological processes are the ones in which living organisms and their body functions are involved. On the other hand, pathological processes are certain invasions which are conducted by microorganisms which are pathogenic in nature. Often certain diseases are diagnosed when certain abnormalities in the body fluids are identified. The contribution of HO is in the form of HO-1.

When inflammations are caused in the vascular walls which are formed through lipids and inflammatory cells then the process is called atherosclerosis (Yannarelli. and et. al., 2006). The role of HO-1 is like a protector from vascular inflammations. Since heme groups are produced with an oxidised effect, the heme oxygenase becomes an antioxidant and an anti-inflammatory agent which protects from different types of inflammations in the vascular cells. There are some other roles or functions through which this compound helps in guarding the human body cells and these include antiapoptotic, antiproliferative and immunomodulatory. The basic purpose behind protection is to reduce the effect of atherogenesis (Li, Wang and Vanhoutte, 2012).

The production of this enzyme is witnessed at lower levels. There are certain processes which can be implied for up-regulating the occurrence of HO compound (Lin and et. al., 2010). The enzyme is also involved in the catabolism of heme. Moreover, HO-1 which is expressed at lower levels can be induced in tissues with the help of different stimuli. The role of this compound is realised in situations likely ischemia, hypoxia, hyperoxia, hyperthermia and radiation. The compound is also essential in the process of homeostasis (Choi and Alam, 1996). Overall, the function of this enzyme or compound is to protect the body from vascular injuries and also help in aiding the inflammatory processes.

Ways in which naturally occurring compounds can be utilised for up-regulating heme oxygenase

The HO compound can be up-regulated in the presence of proatherogenic stimuli. As discussed before, the role of heme oxygenase is witnessed more in the protection of the body from vascular injuries (Gaedeke, Noble and Border, 2005). The compound has also been important in applications in the branch of pulmonary medicine. The activity of heme oxygenase is measured when isometric tensions are witnessed in situations where the production of oxygen has to be initiated and the use of iron and carbon monoxide is felt (Young-Myeong, 2011). It is important for the anti-inflammatory processes to enhance the production of HO compounds. Apart from iron compounds, there are some more elemental species which are produced after the breaking down of iron composition takes place.

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The activity of heme oxygenase has been augmented in the hemin treatment. The process of up-regulation of the HO compound helps in the maturation and mineralisation of osteoblasts (Gaedeke, Noble and Border, 2005). The involvement of this enzyme in vascular diseases and inflammations has given a lot of importance to the entire inflammatory conditions. Biliverdin is also a compound which is produced when this enzyme gets involved in the catalytic process of the breakdown of heme. The iron compound being an antioxidant forms the oxidised bonds in the iron and carbon monoxide by-products (Choi and Alam, 1996). The induction of HO-1 helps inhibit the maturation of osteoblasts which are included in the mineralisation of bone nodules. As a result, alkaline activities with phosphatase compounds are observed in the entire process.

The entire vascular health is dependent on the balance between vascular walls and the antioxidant mechanisms (Harju and et. al., 2002). The risk factor which is often created in the entire inflammation process is regulated and rehabilitated when such enzymes are reportedly produced naturally. The up-regulation activity of HO is useful in controlling the inflammatory conditions of diabetes and chronic obesity. TNF-alpha and interleukin are certain types of tumours that occur when levels of cytokines are increased. This is witnessed in the cases of diabetes and obesity (Raju, McCoubrey and Maines, 1997). In such situations, the enzyme heme oxygenase plays its role and produces an antioxidant which helps in reducing the ill effect caused by inflammations.

Suppression of macrophage infiltration and abrogation of oxidative or inflammatory transcripts are some of the processes through which up-regulation of heme oxygenase can be initiated (Poss and Tonegawa, 1997). This will help in reducing the occurrence of tumour molecules and also help in the production of more antioxidants and anti-inflammatory agents. Patients with metabolic syndromes, hypertension, etc. have grown over the past decades. HO system which includes a three-step action and chain of processes helps in producing the antioxidants and reduces the effects of inflammations. Moreover, the up-regulatory processes shall help in devising more immunity or protection from pathogens which often enter the body when a harmful stimuli is addressed (Young-Myeong, 2011). The increased activity of HO can be initiated using hemin treatment. Despite some ill effects like high blood pressure and acute pain, the up-regulation is successfully formulated in the body regarding this compound.


Through this assessment, it is realised that heme oxygenase is an important compound when extraction of inflammatory processes are involved. It is essential that the up-regulation of this compound taking place timely so that there are no consequences in the anti-inflammatory processes. The use of HO is found in catabolism of heme and in the production of antioxidants. The body is protected from vascular cell injuries when heme oxygenase is regulated. It has also been realised that there are three isoforms of this compound which are produced at lower levels and can be up-regulated when stress proteins are excessively released.


Books and Journals

  • Choi, A. M. and Alam, J., 1996. Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. American Journal of respiratory cell and molecular biology, 15(1), pp.9-19.
  • Gaedeke, J., Noble, N. A. and Border, W. A., 2005. Curcumin blocks fibrosis in anti-Thy 1 glomerulonephritis through up-regulation of heme oxygenase 1. Kidney International, 68(5), pp.2042-2049.
  • Gong, X. and et. al., 2013. Anti-inflammatory effects of mangiferin on sepsis-induced lung injury in mice via up-regulation of heme oxygenase-1. The Journal of Nutritional Biochemistry, 24(6), pp.1173-1181.
  • Harju, T. and et. al., 2002. Up-regulation of heme oxygenase-1 in alveolar macrophages of newly diagnosed asthmatics. Respiratory medicine, 96(6), pp.418-423.
  • Kietzmann, T., Samoylenko, A. and Immenschuh, S., 2003. Transcriptional regulation of heme oxygenase-1 gene expression by MAP kinases of the JNK and p38 pathways in primary cultures of rat hepatocytes. Journal of Biological Chemistry, 278(20), pp.17927-17936.
  • Kim, A. N. and et. al., 2010. Up-regulation of heme oxygenase-1 expression through CaMKII-ERK1/2-Nrf2 signalling mediates the anti-inflammatory effect of bisdemethoxycurcumin in LPS-stimulated macrophages. Free Radical Biology and Medicine, 49(3), pp.323-331.
  • Lang, D. and et. al., 2005. Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation. International immunology, 17(2), pp.155-165.
  • Martin, D. and et. al., 2004. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. Journal of Biological Chemistry, 279(10), pp.8919-8929.
  • Paine, A. and et. al., 2010. Signalling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochemical pharmacology, 80(12), pp.1895-1903.
  • Poss, K. D. and Tonegawa, S., 1997. Heme oxygenase 1 is required for mammalian iron reutilization. Proceedings of the National Academy of Sciences, 94(20), pp.10919-10924.
  • Raju, V. S., McCoubrey, W. K. and Maines, M. D., 1997. Regulation of heme oxygenase-2 by glucocorticoids in neonatal rat brain: characterization of a functional glucocorticoid response element. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression, 1351(1), pp.89-104.
  • Xia, Z. W. and et. al., 2007. Heme oxygenase-1 attenuates ovalbumin-induced airway inflammation by up-regulation of Foxp3 T-regulatory cells, interleukin-10, and membrane-bound transforming growth factor-β1. The American Journal of pathology, 171(6), pp.1904-1914.
  • Yannarelli, G. G. and et. al., 2006. Heme oxygenase up-regulation in ultraviolet-B irradiated soybean plants involves reactive oxygen species. Planta, 224(5), pp.1154-1162.
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