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2014 ; 20
(11
): 1743-53
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Signaling function of heme oxygenase proteins
#MMPMID24180238
Dennery PA
Antioxid Redox Signal
2014[Apr]; 20
(11
): 1743-53
PMID24180238
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SIGNIFICANCE: Many reports have underscored the importance of the heme
degradation pathway that is regulated by heme oxygenase (HO). This reaction
releases bile pigments and carbon monoxide (CO), which are important antioxidant
and signaling molecules. Thus, the reaction of HO-1 would have significant
cytoprotective effects. Nevertheless, the importance of this protein goes beyond
its enzymatic action. New evidence outlines significant effects of inactive forms
of the HO-1 protein. RECENT ADVANCES: In fact, the role of the HO protein in
cellular signaling, including transcription factor activation, binding to
proteins, phosphorylation, and modulation of protein function, among others, has
started being elucidated. The mechanism by which the inducible form of HO-1, in
particular, can migrate to various cellular compartments to mediate important
signaling or how and why it binds to key transcription factors and other proteins
that are important in DNA repair is also described in several physiologic
systems. CRITICAL ISSUES: The signaling functions of HO-1 may have particular
relevance in clinical circumstances, including cancer, as redistribution of HO-1
into the nuclear compartment is observed with cancer progression and metastasis.
In addition, along with oxidative stress, the pleiotropic functions of HO-1
modulate antioxidant defense. In organ transplantation, HO and its byproducts
suppress rejection at multiple levels and in sepsis-induced pulmonary
dysfunction, inhaled CO or modulation of HO activity can change the course of the
disease in animals. FUTURE DIRECTIONS: It is hoped that a more detailed
understanding of the various signaling functions of HO will guide therapeutic
approaches for complex diseases.
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