Open AccessRegulation of the Expression of Heme Oxygenase-1: Signal Transduction, Gene Promoter Activation, and Beyond
Author(s) -
María Victoria Medina,
Daiana Sapochnik,
Martín Garcia Solá,
Omar A. Coso
Publication year - 2020
Publication title -
antioxidants and redox signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.277
H-Index - 190
eISSN - 1557-7716
pISSN - 1523-0864
DOI - 10.1089/ars.2019.7991
Subject(s) - biliverdin reductase , heme oxygenase , biology , biliverdin , regulation of gene expression , signal transduction , gene expression , transcription factor , heme , microbiology and biotechnology , post translational regulation , transcriptional regulation , gene , biochemistry , enzyme
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 such as Nrf2 (nuclear factor erythroid 2-related factor 2), AP-1 (activator protein-1), and hypoxia-inducible factor, 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 involves 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 messenger RNA stability play critical roles in changes in HO-1 gene expression levels, involving specific factors, proteins, and microRNAs. All potential targets for diagnosis or treatment of diseases 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 upmost importance for research in this field.