Posttranscriptional and transcriptional regulation of endothelial nitric-oxide synthase during hypoxia: the role of microRNAs

Cellular & Molecular Biology Letters

Anna Janaszak-Jasiecka²  Anna Siekierzycka⁴  Rafal Bartoszewski²  Leszek Kalinowski⁴  James F. Collawn¹  Marcin Woźniak⁴  Sylwia Bartoszewska³  Dawid Lejnowski² 

[1] Department of Cell Biology, Developmental, and Integrative, University of Alabama at Birmingham, Birmingham, USA$$;Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland$$;Department of Inorganic Chemistry, Medical University of Gdansk, Gdansk, Poland$$;Department of Medical Laboratory Diagnostics and Central Bank of Frozen Tissues & Genetic Specimens, Medical University of Gdansk, Gdansk, Poland$$

关键词: eNOS;    ER stress;    Hypoxia;    miRNA;    Nitric oxide;    NO bioavailability;   

DOI  :  10.1186/s11658-016-0017-x

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Understanding the cellular pathways that regulate endothelial nitric oxide (eNOS, NOS3) expression and consequently nitric oxide (NO) bioavailability during hypoxia is a necessary aspect in the development of novel treatments for cardiovascular disorders. eNOS expression and eNOS-dependent NO cellular signaling during hypoxia promote an equilibrium of transcriptional and posttranscriptional molecular mechanisms that belong to both proapoptotic and survival pathways. Furthermore, NO bioavailability results not only from eNOS levels, but also relies on the presence of eNOS substrate and cofactors, the phosphorylation status of eNOS, and the presence of reactive oxygen species (ROS) that can inactivate eNOS. Since both NOS3 levels and these signaling pathways can also be a subject of posttranscriptional modulation by microRNAs (miRNAs), this class of short noncoding RNAs contribute another level of regulation for NO bioavailability. As miRNA antagomirs or specific target protectors could be used in therapeutic approaches to regulate NO levels, either by changing NOS3 mRNA stability or through factors governing eNOS activity, it is critical to understand their role in governing eNOS activity during hypoxa. In contrast to a large number of miRNAs reported to the change eNOS expression during hypoxia, only a few miRNAs modulate eNOS activity. Furthermore, impaired miRNA biogenesis leads to NOS3 mRNA stabilization under hypoxia. Here we discuss the recent studies that define miRNAs’ role in maintaining endothelial NO bioavailability emphasizing those miRNAs that directly modulate NOS3 expression or eNOS activity.

【 授权许可】

Unknown