Related Experiment Video

Updated: Feb 8, 2026

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death
08:26

Saturated Fatty Acids Induce Ceramide-associated Macrophage Cell Death

Published on: October 31, 2017

9.7K

Deletion of the stress-response protein REDD1 promotes ceramide-induced retinal cell death and JNK activation

Weiwei Dai1, William P Miller1, Allyson L Toro1

  • 1Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 20, 2018
PubMed

Insights

Western diet consumption increases retinal sphingolipids, leading to cell death. The stress-response protein REDD1 normally protects against this, but its absence worsens ceramide-induced retinal damage.

Area of Science:

  • Ophthalmology
  • Metabolic Research
  • Cellular Biology

Background:

  • Dyslipidemia's role in retinal dysfunction is unclear.
  • Diet-induced obesity and pre-type 2 diabetes models are crucial for studying retinal defects.
  • Western diets high in saturated fats and sugars can induce molecular changes in the retina.

Purpose of the Study:

  • To investigate molecular retinal defects caused by a Western diet in an animal model.
  • To elucidate the role of sphingolipids, protein kinase B (Akt), JNK, and REDD1 in diet-induced retinal dysfunction.
  • To understand the signaling pathways involving ceramide (Cer), REDD1, and thioredoxin-interacting protein (TXNIP) in retinal cell death.

Main Methods:

  • Utilized a mouse model of diet-induced obesity/pre-type 2 diabetes.
  • Administered Western diet, palmitate, or C6-ceramide (Cer) to mice and cultured cells (murine and human).
  • Assessed Akt phosphorylation, JNK activation, cell death, REDD1 expression, and TXNIP expression using molecular assays.
  • Employed REDD1 knockdown/deletion and TXNIP knockdown techniques.

Main Results:

  • Western diet increased retinal sphingolipids, decreased Akt phosphorylation, increased JNK activation, and promoted retinal cell death.
  • C6-Cer mimicked these effects in cultured cells, highlighting sphingolipid-mediated signaling.
  • Western diet and C6-Cer increased REDD1 expression; REDD1 loss exacerbated C6-Cer-induced JNK activation and cell death.
  • REDD1 repressed JNK phosphorylation, while TXNIP knockdown attenuated JNK activation and cell death in response to C6-Cer or REDD1 deletion.

Conclusions:

  • Ceramide-induced REDD1 expression acts as a protective mechanism against retinal cell death.
  • REDD1 attenuates TXNIP-dependent JNK activation, thereby preventing retinal cell death.
  • This study proposes a model where REDD1 modulates TXNIP-mediated JNK signaling to protect the retina from diet-induced damage.
Keywords:
apoptosishigh-fat dietretinopathysphingolipidstype 2 diabetes

More Related Videos

Triggering Cell Stress and Death Using Conventional UV Laser Confocal Microscopy10:18

Triggering Cell Stress and Death Using Conventional UV Laser Confocal Microscopy

Published on: February 3, 2017

10.0K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.8K

Related Concept Videos

Responses to Heat and Cold Stress02:45

Responses to Heat and Cold Stress

Every organism has an optimum temperature range within which healthy growth and physiological functioning can occur. At the ends of this range, there will be a minimum and maximum temperature that interrupt biological processes.
14.9K
Responses to Salt Stress02:02

Responses to Salt Stress

Salt stress—which can be triggered by high salt concentrations in a plant’s environment—can significantly affect plant growth and crop production by influencing photosynthesis and the absorption of water and nutrients.
14.6K
Stress Response System01:21

Stress Response System

The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
In the alarm stage, the body's...
914
Psychological Responses to Stress01:20

Psychological Responses to Stress

Psychological responses to stress encompass the various cognitive and emotional reactions individuals experience when faced with challenging or threatening situations, such as a job loss. Prolonged exposure to stressors can disturb emotional balance, increasing negative emotions (e.g., anxiety and sadness) and diminishing positive emotions (e.g., joy and satisfaction). These persistent emotional shifts are associated with an increased risk of both physical illness and mental health issues, such...
720
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
437
The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
18.9K