Related Experiment Video

Updated: Aug 4, 2026

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

10.3K

Inhibition, But Not Depletion, of Erk Signaling Ameliorates Anthracycline-Induced Cardiotoxicity in Zebrafish

Maryam Moossavi1, Ping Zhu1, Yonghe Ding1

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

JACC. Cardiooncology
|October 3, 2025
PubMed
Abstract

Insights

Aberrant extracellular signal-regulated kinase (ERK) activation contributes to anthracycline-induced cardiotoxicity (AIC). Controlled ERK inhibition may offer therapeutic benefits, but excessive inhibition can be cardiotoxic, highlighting the need for careful optimization.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Anthracycline-induced cardiotoxicity (AIC) is a significant limitation in cancer therapy.
  • Extracellular signal-regulated kinase (ERK) signaling is implicated in cardiomyopathy, but its specific role in AIC is unclear.

Purpose of the Study:

  • Investigate the role of ERK signaling in AIC using zebrafish genetics.
  • Evaluate the therapeutic potential of ERK inhibition in AIC.

Main Methods:

  • Utilized a zebrafish model of AIC.
  • Screened genes in ERK signaling pathways and evaluated mutant effects.
  • Conducted pharmacologic studies with ERK inhibitors.

Main Results:

  • Mek1 and Erk1 heterozygous mutants showed protective effects against AIC.
  • Elevated ERK phosphorylation was observed in AIC hearts.
  • Homozygous erk1 mutants and excessive ERK inhibition worsened cardiotoxicity, while low doses were therapeutic.
  • AIC models exhibited accelerated cardiac senescence, which ERK inhibition attenuated.

Conclusions:

  • Aberrant ERK activation contributes to AIC.
  • Controlled ERK inhibition may offer therapeutic benefits through antiaging mechanisms.
  • Optimization of ERK inhibition is crucial to avoid dose-dependent cardiotoxicity.
Keywords:
Erkaginganthracyclinescardiotoxicitysenescencezebrafish

More Related Videos

CRISPR-Cas9-Mediated Precise Knock-In Edits in Zebrafish Hearts06:52

CRISPR-Cas9-Mediated Precise Knock-In Edits in Zebrafish Hearts

Published on: September 13, 2022

3.9K
Author Spotlight: Novel Intraperitoneal Injection Method for Zebrafish Cardiotoxicity Models02:32

Author Spotlight: Novel Intraperitoneal Injection Method for Zebrafish Cardiotoxicity Models

Published on: March 29, 2024

2.8K

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Heart Failure Drugs: Inotropic Agents01:26

Heart Failure Drugs: Inotropic Agents

Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...