Related Experiment Video

Updated: May 14, 2026

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3
08:20

Analysis of Apoptosis in Zebrafish Embryos by Whole-mount Immunofluorescence to Detect Activated Caspase 3

Published on: December 20, 2013

Transcription factor Foxo3a prevents apoptosis by regulating calcium through the apoptosis repressor with caspase

Daoyuan Lu1, Jinping Liu1, Jianqin Jiao1

  • 1Division of Cardiovascular Research, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

The Journal of Biological Chemistry
|February 6, 2013
PubMed

Insights

The transcription factor Foxo3a protects the heart by activating the anti-apoptotic protein ARC, thereby maintaining calcium balance and inhibiting cardiomyocyte apoptosis during heart disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cell Death Mechanisms

Background:

  • Apoptosis is implicated in myocardial infarction and heart failure.
  • The role of transcription factor Foxo3a in cardiac apoptosis requires further clarification.
  • Apoptosis repressor with caspase recruitment domain (ARC) is a known anti-apoptotic protein.

Purpose of the Study:

  • To elucidate the role of Foxo3a in regulating cardiac apoptosis.
  • To investigate the interplay between Foxo3a, ARC, and calcium homeostasis in cardiomyocytes.
  • To determine if Foxo3a regulates ARC expression.

Main Methods:

  • Investigated the effects of Foxo3a expression and knockdown on cardiomyocyte apoptosis.
  • Assessed the role of ARC in regulating calcium levels under oxidative stress.
  • Utilized Foxo3a knockout and ARC transgenic mouse models.
  • Performed experiments to determine if Foxo3a directly binds to the ARC promoter.

Main Results:

  • Enforced Foxo3a expression inhibited cardiomyocyte apoptosis; Foxo3a knockdown sensitized cells to apoptosis.
  • ARC attenuated calcium release from the sarcoplasmic reticulum and inhibited oxidative stress-induced calcium elevations.
  • Foxo3a maintained calcium homeostasis via ARC.
  • Foxo3a knockout mice showed larger myocardial infarction sizes; ARC transgenic mice had reduced infarct size and balanced calcium levels.
  • Foxo3a directly activated ARC expression by binding to its promoter.

Conclusions:

  • Foxo3a maintains calcium homeostasis and inhibits cardiac apoptosis by trans-activating the ARC promoter.
  • Foxo3a and ARC form a novel anti-apoptotic pathway regulating cardiac calcium homeostasis.
  • This pathway is crucial for protecting the heart against pathological conditions like myocardial infarction.

More Related Videos

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor06:26

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...