Related Experiment Video

Updated: Aug 15, 2026

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
08:22

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model

Published on: October 27, 2020

Role of apoptosis-inducing factor in myocardial cell death by ischemia-reperfusion

Gi-Tae Kim1, Yang-Sook Chun, Jong-Wan Park

  • 1Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea.

Biochemical and Biophysical Research Communications
|September 10, 2003
PubMed

Insights

Apoptosis-inducing factor (AIF) drives heart cell death after ischemia-reperfusion injury. This process, independent of caspase-3, is reduced by ischemic preconditioning, suggesting a key role for AIF in heart attack recovery.

Area of Science:

  • Cardiovascular Biology
  • Cell Death Mechanisms
  • Molecular Cardiology

Background:

  • Myocardial cell death during ischemia-reperfusion injury is a significant clinical concern.
  • The precise molecular pathways driving apoptosis in the heart remain incompletely understood.
  • Apoptosis-inducing factor (AIF) is a known caspase-independent cell death effector, translocating from mitochondria to the nucleus.

Purpose of the Study:

  • To investigate the role of AIF in myocardial cell death following ischemia-reperfusion injury in isolated rat hearts.
  • To determine if AIF-dependent apoptosis contributes to cardiac damage and if it is modulated by ischemic preconditioning.

Main Methods:

  • Isolated rat hearts were subjected to ischemia-reperfusion protocols.
  • Western blotting and subcellular fractionation were used to detect AIF localization (mitochondrial, cytosolic, nuclear).
  • Pulse-field gel electrophoresis assessed DNA fragmentation, and caspase-3 activation/cytochrome c release were evaluated.

Main Results:

  • AIF translocated from mitochondria to cytosolic and nuclear fractions following ischemia-reperfusion.
  • AIF release and 50 kbp DNA fragmentation increased in a reperfusion time-dependent manner.
  • Significant cytochrome c release or caspase-3 activation was not observed; ischemic preconditioning attenuated AIF release and DNA fragmentation.

Conclusions:

  • AIF-dependent apoptosis is a likely mechanism of myocardial cell death in ischemia-reperfusion injury.
  • The findings highlight AIF as a potential therapeutic target for protecting the heart during reperfusion.
  • Ischemic preconditioning exerts protective effects, at least partly, by inhibiting AIF-mediated cell death pathways.

More Related Videos

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury07:23

Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury

Published on: March 7, 2022

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke11:32

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke

Published on: January 3, 2025

Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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...
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...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...