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Antioxid Redox Signal. 2019 Dec 20. doi: 10.1089/ars.2019.7991. [Epub ahead of print]

Regulation of the Expression of Heme Oxygenase-1. Signal Transduction, Gene Promoter Activation and Beyond.

Author information

1
Universidad de Buenos Aires Facultad de Ciencias Exactas y Naturales, 117139, Departamento de Fisiología, Biología Molecular y Celular , Ciudad Autonoma de Buenos Aires, Argentina.
2
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE) - CONICET - Universidad de Buenos Aires , Ciudad Autonoma de Buenos Aires, Argentina; victoriamedina91@gmail.com.
3
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE) - CONICET - Universidad de Buenos Aires, , Ciudad Autonoma de Buenos Aires, Argentina; daianasapochnik@gmail.com.
4
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE) - CONICET - Universidad de Buenos Aires , Ciudad Autonoma de Buenos Aires, Argentina; megarciasola@gmail.com.
5
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE) - CONICET - Universidad de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina; ocoso@fbmc.fcen.uba.ar.

Abstract

SIGNIFICANCE:

Heme oxygenase 1 (HO-1) is a ubiquitous 32-kDa protein expressed in many tissues and highly inducible. They catalyze the degradation of the heme group and the release of free iron, carbon monoxide and biliverdin, the latter converted to bilirubin by biliverdin reductase. Its role in the regulation of cellular homeostasis is widely documented. Studying regulation of HO-1 expression is important not only to understand the life of healthy cells but also the unbalances in cell metabolism that lead to disease. Recent Advances: The regulation of its enzymatic activity depends heavily upon changes in expression studied mainly at the transcriptional level. Current knowledge regarding HO-1 gene expression focuses primarily on transcription factors like Nrf2, AP-1 and HIF which collect signal transduction pathway information at the HO-1 gene promoter. Understanding of gene expression regulation is not limited to transcription factor activity but also consider an extended range of post or cotranscriptional regulated events.

CRITICAL ISSUES:

In addition to the regulation of gene promoter activity, alternative splicing, alternative polyadenylation and regulation of mRNA stability play critical roles in changes in HO-1 gene expression levels, involving of specific factors, proteins and miRNAs. All potential targets for diagnosis or treatment of diseases that are related to HO-1 dysregulation.

FUTURE DIRECTIONS:

Unbalances in the tightly regulated gene expression mechanisms lead to cell transformation and cancer development. Knowledge of these events and signal transduction cascades triggered by oncogenes in which HO-1 plays a critical role is of the upmost importance for research in this field.

PMID:
31861960
DOI:
10.1089/ars.2019.7991

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