Nuclear Heme Oxygenase-1 (HO-1) Modulates Subcellular Distribution and Activation of Nrf2, Impacting Metabolic and Anti-oxidant Defenses

Abstract

Background: A 28-kDa HO-1 isoform is induced by oxidative stress and cancer and accumulates in the nucleus. Results: Nuclear HO-1 interacts with Nrf2 and alters expression of its target genes. Conclusion: HO-1 modulates Nrf2 function. Significance: Exploiting the synergistic benefits of the HO-1⅐Nrf2 protein complex is important for developing therapeutic strategies against oxidative stress or cancer.

Heme Oxygenase-1 Promotes Neuron Survival through Down-Regulation of Neuronal NLRP1 Expression after Spinal Cord Injury

“…Based on the fact that cytosolic HO-1 is able to translocate into the nuclei of certain tumor cells [75][76][77], it is possible that HO-1 could directly act as a transcription suppressor or indirectly regulate some transcription factors to inhibit ATF4 expression. It has been reported that HO-1 modulates subcellular distribution and activation of Nrf2 [75], suggesting HO-1 is able to influence the activity of certain transcription factors. However, in our study, HO-1 seems to be located only in the cytosol, excluding its effect in the nucleus.…”

Anti-inflammatory Activity of β-Carotene, Lycopene and Tri-n-butylborane, a Scavenger of Reactive Oxygen Species

“…Macrophages are resistant to relatively high concentrations of heme in comparison to endothelial cells, and have constitutively high expression of heme oxygenase 1 (HMOX1) to protect against heme toxicity (14,15). As an antioxidant stress protein, HMOX1 is expressed in almost all cells and tissues, and is highly upregulated by heme or other stress stimuli to provide protection against oxidative damage and apoptosis (16).…”

“…As an antioxidant stress protein, HMOX1 is expressed in almost all cells and tissues, and is highly upregulated by heme or other stress stimuli to provide protection against oxidative damage and apoptosis (16). This is a protective and adaptive response inherent to most tissues (14). The cytoprotective effects of HMOX1 have been attributed to its enzymatic action in heme degradation and also its catalytic byproducts such as carbon monoxide and biliverdin (17).…”

Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

“…HO-1 is an antioxidative enzyme (14) but may also act independently of enzymatic activity, via interaction with several nuclear proteins (13). As HO-1 was present both in cytoplasm and nucleus of RMS cells (Fig.…”

“…HO-1 degrades heme to produce biliverdin, ferrous ion and carbon monoxide (CO) or can act trough protein-protein interaction with Nrf2 transcription factor (13,14). The mechanism underlying the antimyogenic effect of HO-1 in myoblasts is CO-dependent inhibition of C/EBPd binding to the myoD promoter that decreases myoD expression.…”