Related Experiment Video

Updated: Apr 19, 2026

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
08:00

Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity

Published on: July 10, 2019

6.7K

Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO

Qiang Li1, Ping Wang1, Keqiang Ye2

  • 1Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.

Proceedings of the National Academy of Sciences of the United States of America
|January 7, 2015
PubMed

Insights

Nitric oxide (NO) protects the heart by up-regulating the Deleted in colorectal cancer (DCC) receptor. Inhibiting E3 ligases SIAH1 and SIAH2 enhances this cardioprotective effect, offering a potential therapy for myocardial infarction.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Signaling

Background:

  • The Deleted in colorectal cancer (DCC) receptor mediates netrin-1's cardioprotective effects.
  • Netrin-1 signaling is crucial for sustaining nitric oxide (NO) production, enhancing heart protection.

Purpose of the Study:

  • Investigate novel mechanisms of netrin-1-induced DCC upregulation.
  • Elucidate the role of E3 ubiquitin ligases in DCC degradation and netrin-1-dependent cardioprotection.

Main Methods:

  • Utilized siRNA to inhibit SIAH1 and SIAH2 expression in cardiac ischemia/reperfusion models.
  • Assessed infarct size and cardiac function post-treatment.
  • Examined the effect of SIAH inhibition in DCC-deficient mice.

Main Results:

  • Nitric oxide (NO) reduces the expression of E3 ubiquitin ligase SIAH, preventing DCC degradation and increasing DCC levels.
  • Combined inhibition of SIAH1 and SIAH2 significantly reduced infarct size and improved cardiac function after ischemia/reperfusion injury.
  • The protective effects were dependent on DCC expression and were augmented by netrin-1 signaling.

Conclusions:

  • Identified SIAH as a novel therapeutic target for enhancing NO/netrin-1-dependent cardioprotection via the DCC receptor.
  • Combination therapy with netrin-1 and SIAH RNA interference shows promise for treating myocardial infarction.
Keywords:
DCCSIAHcardioprotectionnetrin-1nitric oxide

More Related Videos

Modeling Paracrine Noncanonical Wnt Signaling In Vitro11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

2.0K
Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology10:41

Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology

Published on: January 23, 2021

8.7K

Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.2K
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...
4.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.3K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.8K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.9K