C/EBP transcription factors regulate NADPH oxidase in human aortic smooth muscle cells

Simona-Adriana Manea1, Andra Todirita, Monica Raicu

  • 1Molecular and Cellular Pharmacology - Functional Genomics Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, Bucharest, Romania.

Insights

CCAAT/enhancer-binding proteins (C/EBP) regulate NADPH oxidase (Nox) in vascular smooth muscle cells under inflammation. Targeting C/EBP pathways may counteract oxidative stress in atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Signaling

Background:

  • Oxidative stress and vascular smooth muscle cell (SMC) dysfunction are key in atherosclerosis.
  • NADPH oxidase (Nox) enzymes are implicated in SMC dysfunction, but their regulation is not fully understood.
  • CCAAT/enhancer-binding proteins (C/EBP) are known regulators of cellular processes and inflammation.

Purpose of the Study:

  • To investigate the role of C/EBP transcription factors in regulating Nox expression and activity in human aortic SMCs.
  • To elucidate the mechanisms by which C/EBP proteins influence Nox enzymes under pro-inflammatory conditions.

Main Methods:

  • Human aortic SMCs were treated with interferon-γ (IFN-γ).
  • Assays included lucigenin-enhanced chemiluminescence, real-time PCR, Western blot, promoter-luciferase reporter assays, and chromatin immunoprecipitation.
  • C/EBP silencing and overexpression studies were performed.

Main Results:

  • IFN-γ induced Nox activity, expression, and C/EBPα, C/EBPβ, and C/EBPδ protein levels in SMCs.
  • Silencing C/EBP factors differentially reduced IFN-γ-induced Nox activity and expression.
  • C/EBP proteins physically interacted with Nox1, Nox4, and Nox5 promoters, enhancing their activity.

Conclusions:

  • C/EBP transcription factors are critical regulators of Nox enzymes in IFN-γ-stimulated SMCs.
  • C/EBP activation may lead to excessive reactive oxygen species production, contributing to atherosclerosis.
  • Targeting C/EBP signaling pathways offers a potential therapeutic strategy against oxidative stress in atherosclerosis.

Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.3K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.5K
Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
3.8K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.1K