Heme Oxygenase 1 in Vertebrates: Friend and Foe

Abstract

HO-1 is the inducible form of the enzyme heme-oxygenase. HO-1 catalyzes heme breakdown, reducing the levels of this important oxidant molecule and generating antioxidant, anti-inflammatory, and anti-apoptotic byproducts. Thus, HO-1 has been described as an important stress response mechanism during both physiologic and pathological processes. Interestingly, some findings are demonstrating that uncontrolled levels of HO-1 byproducts can be associated with cell death and tissue destruction as well. Furthermore, HO-1 can be located in the nucleus, influencing gene transcription, cellular proliferation, and DNA repair. Here, we will discuss several studies that approach HO-1 effects as a protective or detrimental mechanism in different pathological conditions. In this sense, as the major organs of vertebrates will deal specifically with distinct types of stresses, we discuss the HO-1 role in each of them, exposing the contradictions associated with HO-1 expression after different insults and circumstances.

BAK knockdown delays bleaching and alleviates oxidative DNA damage in a reef-building coral

“…Heme oxygenase 1 is an inducible form of heme oxygenase enzyme that catalyzes heme breakdown. Its byproducts possess anti-inflammatory, anti-apoptotic, and antioxidant properties and a truncated form of HO-1 with low enzymatic activity acts as a transcriptional factor in the nucleus during stress response (reviewed in ( 37 )). OGG1 can also induce gene transcription, although the mechanisms remain largely unclear ( 36 ).…”

“…Bcl-2 expression can be controlled by the Nrf2 pathway (41) but overexpression of Heme oxygenase 1 is enough to induce the expression of Bcl-2 in a rat heart, suggesting HO-1 might be an intermediary in the regulation (42). Additionally, HO-1 can regulate the expression of Nrf2 in what appears to be a positive feedback loop (37) which points to a complex regulatory network surrounding the Nrf2 stress-response pathway. Nrf2 is a pleiotropic factor, and it may thus play a major role in acclimatization to environmental stress in corals with improved symbiosis stability impacting multiple important defense mechanisms in the organism.…”

Bilirubin Concentration in Follicular Fluid Is Increased in Infertile Females, Correlates with Decreased Antioxidant Levels and Increased Nitric Oxide Metabolites, and Negatively Affects Outcome Measures of In Vitro Fertilization

“…As previously mentioned, intracellular heme catabolism is mainly dependen activity of HOx, the enzymes catalyzing the rate-limiting reaction of heme degr HO exists in two isoforms: heme oxygenase 1 (HO-1) and heme oxygenase 2 Whilst HO-2 is constitutively expressed in all human tissues (although in d amounts), HO-1 is the inducible isoenzyme that can be found in a lower number o [16,17]. The expression of HO-1 is modulated by that of the nuclear factor eryt related factor 2 (Nrf2), activating the cell defense systems (including HO-1) a variety of stressors [18][19][20].…”

“…HO exists in two isoforms: heme oxygenase 1 (HO-1) and heme oxygenase 2 (HO-2). Whilst HO-2 is constitutively expressed in all human tissues (although in different amounts), HO-1 is the inducible isoenzyme that can be found in a lower number of tissues [16,17].…”

Absence of Heme Oxygenase-1 Affects Trophoblastic Spheroid Implantation and Provokes Dysregulation of Stress and Angiogenesis Gene Expression in the Uterus

“…It catalyzes the degradation of free heme into carbon monoxide (CO), free iron (Fe 2+ ) and biliverdin [ 3 ]. HO-1 is ubiquitously expressed in most tissues across multiple species [ 4 ] and plays a crucial physiological protective role [ 5 ]. Various stimuli, such as heme, heat shock, heavy metals and cytokines, induce this enzyme in response to oxidative stress [ 3 ].…”