Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

How do cells respond to their thermal environment?

James R Lepock1

  • 1Department of Medical Biophysics and the Ontario Cancer Institute, University of Toronto, Ontario, Canada.

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
|December 13, 2005
PubMed
Summary

Heat shock triggers cellular responses like thermotolerance and radiosensitization. Protein denaturation, not time at temperature, determines whether cells activate protective mechanisms or undergo inactivation and damage.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Multiphoton ANS fluorescence microscopy as an in vivo sensor for protein misfolding stress.

Cell stress & chaperones·2011
Same author

Unfolding and folding kinetics of amyotrophic lateral sclerosis-associated mutant Cu,Zn superoxide dismutases.

Journal of molecular biology·2008
Same author

Novel chemical enhancers of heat shock increase thermal radiosensitization through a mitotic catastrophe pathway.

Cancer research·2007
Same author

Equilibrium thermodynamic analysis of amyotrophic lateral sclerosis-associated mutant apo Cu,Zn superoxide dismutases.

Biochemistry·2006
Same author

Simultaneous two-photon excitation of photofrin in relation to photodynamic therapy.

Photochemistry and photobiology·2006
Same author

Calorimetric analysis of thermodynamic stability and aggregation for apo and holo amyotrophic lateral sclerosis-associated Gly-93 mutants of superoxide dismutase.

The Journal of biological chemistry·2006

Area of Science:

  • Cellular Biology
  • Biophysics
  • Stress Response

Background:

  • Cells respond to heat shock with both activating (thermotolerance) and inactivating (cytotoxicity, radiosensitization) mechanisms.
  • The magnitude of temperature change influences the dominant cellular response.
  • Biomedical interest lies in understanding these heat shock responses and their underlying triggers.

Purpose of the Study:

  • To investigate the common molecular trigger for heat shock-induced activating and inactivating cellular responses.
  • To determine whether protein denaturation or time at temperature is the primary determinant of cellular fate after heat shock.

Main Methods:

  • Analysis of activation energies for thermotolerance, heat cytotoxicity, and radiosensitization.
  • Investigation of the role of protein denaturation and aggregation in triggering cellular responses.

Related Experiment Videos

  • Examination of the involvement of heat shock proteins (HSP90) and heat shock factor 1 (HSF1) in the response pathway.
  • Correlation of protein denaturation levels with cellular outcomes (survival, sensitization).

    • Main Results:

    • Similar activation energies (120-146 kcal/mol) suggest a common molecular trigger for thermotolerance, cytotoxicity, and radiosensitization.
    • Protein denaturation is identified as the critical trigger, with low levels activating HSP90 and HSF1 for thermotolerance.
    • Severe heat shock causes increased protein denaturation and aggregation, leading to inactivation of vital cellular processes and cell death or sensitization.
    • Cellular fate is governed by the summation of activation and inactivation events, dictated by the extent of protein denaturation and aggregation.

    Conclusions:

    • Heat-induced protein denaturation, not merely time at temperature, is the primary determinant of cellular response to heat shock.
    • Stabilizing proteins against denaturation enhances activating responses, while sensitizing them promotes inactivating responses.
    • Understanding protein denaturation is key to modulating cellular responses to thermal stress and related treatments.