# Translational Control by Osmotically Active Solutes

> **NIH NIH R37** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $582,358

## Abstract

The cellular response to nutritional and environmental stress has been associated with the
pathology of many diseases. Major contributors to cell fate decisions in response to stress are: (i)
cell-type specific factors, (ii) time and (iii) intensity of stress. Chronic and high intensity stress
conditions attenuate survival and favor apoptosis. The best-studied physiological stress
conditions that are related to human disease are endoplasmic reticulum (ER) stress, which is
caused by the accumulation of unfolded proteins in the ER (diabetes, obesity, cancer) and
oxidative stress, which results in increased reactive oxygen species (R08) and disruption of
physiological R08 Signaling (neurodegeneration). Hypeosmotic stress is less-well studied.
However, the major pathology with hyperosmotic stress is induction of the inflammatory response
via increased expression of NF-kB target genes. The mechanisms that control inflammation and
cellular recovery from hypeosmotic stress and specifically regulation of mRNA translation are not
known. Because cells activate survival and apoptotic signals in response to stress, the interplay
between these competing signals is crucial for elucidating adaptation and death mechanisms. We
propose to study:
1. The functions of recently discovered cytoplasmic RNA-protein complexes in the response to
hyperosmotic stress
2. Test the hypothesis that oxidation of cysteines drives HnRNPA 1 out of the nucleus during
hyperosmotic stress and this cytoplasmic accumulation promotes apoptosis via translational
control mechanisms.
3. The mechanisms of translational control during hyperosmotic stress. We propose a novel
mechanism that controls ribosomal subunit availability and function that involves induction of
autophagy
4. The mechanism via which the signaling of elF2α phosphorylation inhibits adaptation and
promotes inflammatory mechanisms in response to hyperosmotic cells.

## Key facts

- **NIH application ID:** 9908062
- **Project number:** 5R37DK060596-19
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** MARIA HATZOGLOU
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $582,358
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908062

## Citation

> US National Institutes of Health, RePORTER application 9908062, Translational Control by Osmotically Active Solutes (5R37DK060596-19). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9908062. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*