Posttranscriptional and transcriptional regulation of endothelial nitric-oxide synthase during hypoxia: the role of microRNAs. 2016

Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
Department of Medical Laboratory Diagnostics and Central Bank of Frozen Tissues & Genetic Specimens, Medical University of Gdansk, Debinki 7, 80-211 Gdansk, Poland.

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.

UI MeSH Term Description Entries
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D052250 Nitric Oxide Synthase Type III A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in ENDOTHELIAL CELLS. ECNOS Enzyme,ENOS Enzyme,Endothelial Constitutive Nitric Oxide Synthase,Endothelial Nitric Oxide Synthase,Nitric Oxide Synthase, Type III
D035683 MicroRNAs Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing. RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA

Related Publications

Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
November 2006, American journal of physiology. Cell physiology,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
October 1999, Circulation research,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
June 1996, The Journal of biological chemistry,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
February 2000, Circulation research,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
September 2004, Circulation research,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
June 1998, The Journal of biological chemistry,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
September 2000, American journal of physiology. Lung cellular and molecular physiology,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
February 2001, American journal of physiology. Renal physiology,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
May 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
Leszek Kalinowski, and Anna Janaszak-Jasiecka, and Anna Siekierzycka, and Sylwia Bartoszewska, and Marcin Woźniak, and Dawid Lejnowski, and James F Collawn, and Rafal Bartoszewski
January 1997, Trends in cardiovascular medicine,
Copied contents to your clipboard!