Evidences a(CHEBI:heme) to p(HGNC:HMOX1)

Free heme is a dangerous molecule which can be recognized and degenerated by stress-responsive enzyme oxygenase- 1 (HO-1) [16] which plays an essential role in host defense against heme.

Lysis of red blood cells with consequent increases in free heme most likely caused the increase in HO-1 activity responsible for increased COHb concentrations, which is similar to that observed with circulatory devices [6].

Importantly, heme b interaction with heme oxygenase (HO; Lad et al., 2003), the enzyme responsible for heme intracellular catabolism, and hemopexin (Hx; Paoli et al., 1999), a plasmatic heme scavenger, is essential for the regulation of free heme availability and Fe recycling (Kovtunovych et al., 2010; Tolosano et al., 2010).

Consistently, CD11b cells (granulocytes and monocytes) and iron-rich cells (macrophages) isolated from heme-treated Hx-null mice show a higher heme content and increased mRNA and protein expression of HO-1, Lferritin, and Fpn (Figure 1B-G) and elevated mRNA levels of the proinflammatory cytokine IL-6 ( Figure 1H).

In agreement with the electrical cell–substrate impedance sensing data described above, the proteome changes triggered by 10 μM heme were indicative of an adaptive response with prominent induction of HMOX1 and ferritin light (FTL) and heavy (FTH1) chains (Figure 5d,left panel).

Despite its damaging effects, heme induces the expression of HO-1, which degrades heme to anti-inflammatory, cytoprotective, and antioxidant products [25].

A recent Phase IIB clinical trial showed that preconditioning using hemin upregulated HO-1 in renal transplantation, launching further studies on clinical outcome [97].

CD163 mediated hemoglobin/hematoma clearance is involved in the induction of HO-1, a rate-limiting enzyme for heme degradation 26.

As predicted, HMOX1 expression levels (means 6 SD) in hemin-treated cells were much higher (7.25 6 5.02, n = 12; P , 0.001) than in nontreated controls (0.14 6 0.18, n = 9) or A1AT-treated cells (0.09 6 0.1, n = 9).

In the extravascular compartment, cellular heme oxygenase (HO) is the most essential heme degrading protein, converting heme to free iron, biliverdin and CO [26,27].

Upon degradation of RBCs in the erythrophagosome, heme is imported into the cytoplasm for degradation by the heme-degrading enzyme heme oxygenase-1 (HMOX1) [7].

A major intracellular antioxidant is heme oxygenase-1 (HO-1) which, through its heme-degrading activity, plays a critical role in the protection of cells.

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.