# MODULATORS OF CELLULAR HEAT SENSITIVITY

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 1992 · $176,966

## Abstract

Protective and adaptive responses of cells to injury are essential to
survival and reproduction of all biological systems. Cancer cells are
known to utilize adaptive mechanisms, often with adverse effects on
therapeutic outcome, e.g., multidrug resistance. The cellular stress
response is a major aspect of cellular adaptation to both disease and to
therapy, and has been increasingly implicated in a wide spectrum of
disease processes, including those leading to cancer. A highly conserved
set of heat shock proteins (HSPs), part of the cellular stress response,
therefore, have become the focus of many scientific studies in recent
years. Our ongoing research has identified a major novel aspect of the
cellular stress response that needs to be understood in the context of
HSPs and cellular adaptation mechanisms.

The focus of our project is the role of protein glycosylation in the
cellular stress response. Cells that are stressed by hyperthermia, are
known to increase the synthesis of major HSPs,while developing a
transient state of heat resistance, known as thermotolerance.
Concurrently, they show increased activity of certain
glycosyltransferases and increased synthesis of specific glycoproteins,
e.g., GP50. We hypothesize that both stress-induced glycoproteins and
major HSPs are essential for cellular adaptation and the full expression
of thermotolerance. Other stress conditions such as hypoxia, and
treatments with peroxides, also activate a stress response that include
elements of the heat shock response, and lead to the expression of
tolerance.

Specific Aims are directed at the major heat-induced glycosylation
product, i.e., the 50 Kd glycoprotein GP50. The proposed research will
examine: AIM 1) the structure of GP50, Aim 2) its function and its
contribution to the expression of thermotolerance. Functional studies
will utilize microinjection techniques, and a rare mutant in O-linked
glycosylation. Aim 3) Another major objective is the characterization of
glycosylation and HSP synthesis induced by hypoxia and by hydrogen
peroxide, as well as their functional consequences to cell survival
under stress conditions.

Understanding mechanisms of the general stress response offers potential
applications in many areas of medicine. In oncology, adjunct use of
hyperthermia with drugs and X-irradiation continues to be supported by a
strong biological rationale, while stress responses induced by
hypoxia/reoxygenation are relevant to not only to tumors, but also to
injury following infarcts and transient hypoxia in various organ
systems.

## Key facts

- **NIH application ID:** 3171297
- **Project number:** 2R01CA033405-12
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **SAM.gov UEI:** VDFYLZPJEAV6
- **Principal Investigator:** KURT J HENLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $176,966
- **Award type:** 2
- **Project period:** 1981-12-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171297

## Citation

> US National Institutes of Health, RePORTER application 3171297, MODULATORS OF CELLULAR HEAT SENSITIVITY (2R01CA033405-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171297. Licensed CC0.

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