New Insights into Intracellular Locations and Functions of Heme Oxygenase-1

Abstract

Significance: Heme oxygenase-1 (HMOX1) plays a critical role in the protection of cells, and the inducible enzyme is implicated in a spectrum of human diseases. The increasing prevalence of cardiovascular and metabolic morbidities, for which current treatment approaches are not optimal, emphasizes the necessity to better understand key players such as HMOX1 that may be therapeutic targets. Recent Advances: HMOX1 is a dynamic protein that can undergo post-translational and structural modifications which modulate HMOX1 function. Moreover, trafficking from the endoplasmic reticulum to other cellular compartments, including the nucleus, highlights that HMOX1 may play roles other than the catabolism of heme. Critical Issues: The ability of HMOX1 to be induced by a variety of stressors, in an equally wide variety of tissues and cell types, represents an obstacle for the therapeutic exploitation of the enzyme. Any capacity to modulate HMOX1 in cardiovascular and metabolic diseases should be tempered with an appreciation that HMOX1 may have an impact on cancer. Moreover, the potential for heme catabolism end products, such as carbon monoxide, to amplify the HMOX1 stress response should be considered. Future Directions: A more complete understanding of HMOX1 modifications and the properties that they impart is necessary. Delineating these parameters will provide a clearer picture of the opportunities to modulate HMOX1 in human disease. Antioxid. Redox Signal. 20: 1723-1742.

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“…HO-1 and HO-2 both are localized to the endoplasmic reticulum (ER). In addition, HO-1 is found in mitochondria, nucleus and plasma membrane caveolae (Dunn et al 2014). The presence of HO-1 in the nuclei and mitochondria suggests HO-1 has the functions other than degradation of heme (Dunn et al 2014).…”

“…In addition, HO-1 is found in mitochondria, nucleus and plasma membrane caveolae (Dunn et al 2014). The presence of HO-1 in the nuclei and mitochondria suggests HO-1 has the functions other than degradation of heme (Dunn et al 2014). HO-1 expression is controlled by its own substrate (heme) though interaction with Bach1 repressor protein (Igarashi and Watanabe-Matsui 2014).…”

“…Bilirubin and CO mediate protective effects of HO-1 induction: Protective effects of HO-1 induction are often attributed to its role in breakdown of pro-oxidant heme and in the generation of bile pigments (biliverdin and bilirubin) and carbon monoxide (CO) (reviewed in Dunn et al 2014). In an adult human, a total of 400 mg bilirubin is produced per day (Khan and Quigley 2011).…”

“…The therapeutic efficacy of these drugs may be linked, at least in part, to HO-1 induction (reviewed in Dunn et al 2014). HO-1 expression in human renal cancer cells was induced by anti-renal cancer drugs rapamycin and sorafenib (Banerjee et al 2012).…”

A szabadidős mozgás kardiovaszkuláris és vastagbélgyulladást csökkentő hatása patkányban: a hem-oxigenáz és a nitrogénmonoxid-szintáz enzimek szerepe

“…A HO-1 sejten belül több sejtalkotóban előfordulhat, az endoplazmatikus retikulumban, a kaveolákban és a mitokondriumban egy hidrofób transzmembrán szegmens a citokróm P450 reduktázzal és a biliverdin reduktázzal együtt kihorgonyozza a membránhoz. Stressz hatására a transzmembrán domén lehasításával a megrövidült enzim a citoplazmába vagy a sejtmagba kerül (Dunn, Midwinter et al 2014). A HO-1 izoforma transzkripcióját, melyet hősokk protein 32-nek is neveznek, számos tényező képes indukálni: pl.…”