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Related Concept Videos

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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.
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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...
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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.
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Related Experiment Video

Updated: Feb 17, 2026

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
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A Unique ISR Program Determines Cellular Responses to Chronic Stress.

Bo-Jhih Guan1, Vincent van Hoef2, Raul Jobava1

  • 1Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.

Molecular Cell
|December 9, 2017
PubMed
Summary
This summary is machine-generated.

Chronic endoplasmic reticulum (ER) stress triggers a unique integrated stress response (ISR) program. This involves sustained translation of specific mRNAs and gene reprogramming to maintain proteostasis and ER function, preventing disease.

Keywords:
ER stressPERKeIF2eIF2BeIF3integrated stress responsemRNA translationprotein synthesisstress signalingunfolded protein response

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Stress Response

Background:

  • The integrated stress response (ISR) is a cellular defense mechanism against endoplasmic reticulum (ER) stress.
  • Acute ER stress typically involves reduced global protein synthesis followed by recovery.
  • The response to chronic ER stress remains less understood.

Purpose of the Study:

  • To investigate the distinct molecular mechanisms of the ISR during chronic ER stress.
  • To elucidate how cells maintain proteostasis and ER function under prolonged stress.
  • To identify pathways contributing to ER dysfunction-associated diseases.

Main Methods:

  • Analysis of mRNA translation dynamics under chronic ER stress conditions.
  • Investigating the role of the PERK pathway and eIF3 in translational control.
  • Examining transcriptional reprogramming and its impact on protein expression.
  • Assessing the functional consequences on ER proteostasis and cellular phenotype.

Main Results:

  • Chronic ER stress induces a distinct ISR program with sustained upstream open reading frame (uORF) mRNA translation.
  • This program involves a PERK-dependent switch to eIF3-mediated translation initiation, allowing partial recovery of protein synthesis.
  • Simultaneous transcriptional reprogramming selectively upregulates ER-resident proteins, enhancing proteostasis.
  • This coordinated response prevents ER dysfunction and inhibits "foamy cell" formation.

Conclusions:

  • Chronic ER stress activates a unique ISR program characterized by persistent uORF translation and gene expression reprogramming.
  • This adaptive response maintains cellular proteostasis and ER function, preventing disease pathologies.
  • Understanding this chronic ISR program provides insights into diseases linked to ER dysfunction.