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Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke
11:32

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

Published on: January 3, 2025

Increased nuclear apoptosis-inducing factor after transient focal ischemia: a 12/15-lipoxygenase-dependent organelle

Stefanie Pallast1, Ken Arai, Anton Pekcec

  • 1Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|January 14, 2010
PubMed

Insights

12/15-lipoxygenase (12/15-LOX) and apoptosis-inducing factor (AIF) are key in stroke-induced brain damage. Inhibiting 12/15-LOX with baicalein reduces AIF nuclear translocation and neuronal cell death, offering neuroprotection.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pathology

Background:

  • 12/15-lipoxygenase (12/15-LOX) is implicated in acute neuronal injury and edema following middle cerebral artery occlusion (MCAO).
  • Apoptosis-inducing factor (AIF) plays a role in caspase-independent apoptosis and ischemic neuronal cell death.

Purpose of the Study:

  • To investigate the sequential relationship between 12/15-LOX and AIF in stroke-induced neuronal injury.
  • To determine the neuroprotective potential of inhibiting 12/15-LOX in a cellular model of oxidative stress.

Main Methods:

  • Examined the colocalization of AIF and 12/15-LOX in the peri-ischemic cortex of MCAO mice.
  • Utilized a neuronal cell line model subjected to oxidative stress (glutathione depletion).
  • Assessed the effect of the 12/15-LOX inhibitor baicalein on AIF translocation and endoplasmic reticulum (ER) protein dispersion.

Main Results:

  • Increased AIF colocalized with 12/15-LOX in the MCAO mouse brain.
  • Baicalein treatment prevented AIF increase and nuclear localization in MCAO mice.
  • In vitro, baicalein abrogated glutamate-induced AIF nuclear translocation (19.3% vs. 64.0% vs. 11.4%) and ER protein dispersion (31.0% vs. 70.0% vs. 8.0%).

Conclusions:

  • 12/15-LOX activation leads to AIF translocation, contributing to neuronal cell death via organelle damage.
  • 12/15-LOX and AIF act sequentially in a common cell death pathway relevant to stroke.
  • Inhibition of 12/15-LOX demonstrates neuroprotective effects by mitigating AIF-mediated cell death.

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