Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis

Sherilyn A. Gordon, Rosemary A. Hoffman, Richard L. Simmons, Henri Ford

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Objective: To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. Design: Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43°C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, box, and bcl-2 expression was analyzed at various times by the Western blot method. Results: Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T- cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly upregulated box. The expression of p53 peaked at 4 hours and preceded maximal box induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased box levels. Levels of bcl-2 were unaffected. Conclusions: Our data show that lISP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and box expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.

Original languageEnglish (US)
Pages (from-to)1277-1282
Number of pages6
JournalArchives of Surgery
Volume132
Issue number12
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Thymocytes
Radiation
Apoptosis
Clone Cells
T-Lymphocytes
Radiation Effects
DNA Fragmentation
Immunosuppressive Agents
Heat-Shock Proteins
Heating
Cell Death
Radiotherapy
Western Blotting

ASJC Scopus subject areas

  • Surgery

Cite this

Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. / Gordon, Sherilyn A.; Hoffman, Rosemary A.; Simmons, Richard L.; Ford, Henri.

In: Archives of Surgery, Vol. 132, No. 12, 01.01.1997, p. 1277-1282.

Research output: Contribution to journalArticle

Gordon, Sherilyn A. ; Hoffman, Rosemary A. ; Simmons, Richard L. ; Ford, Henri. / Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis. In: Archives of Surgery. 1997 ; Vol. 132, No. 12. pp. 1277-1282.
@article{5a2301de00ed44a0b602041613385453,
title = "Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis",
abstract = "Objective: To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. Design: Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43°C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, box, and bcl-2 expression was analyzed at various times by the Western blot method. Results: Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T- cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly upregulated box. The expression of p53 peaked at 4 hours and preceded maximal box induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased box levels. Levels of bcl-2 were unaffected. Conclusions: Our data show that lISP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and box expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.",
author = "Gordon, {Sherilyn A.} and Hoffman, {Rosemary A.} and Simmons, {Richard L.} and Henri Ford",
year = "1997",
month = "1",
day = "1",
doi = "10.1001/archsurg.1997.01430360023004",
language = "English (US)",
volume = "132",
pages = "1277--1282",
journal = "JAMA Surgery",
issn = "2168-6254",
publisher = "American Medical Association",
number = "12",

}

TY - JOUR

T1 - Induction of heat shock protein 70 protects thymocytes against radiation-induced apoptosis

AU - Gordon, Sherilyn A.

AU - Hoffman, Rosemary A.

AU - Simmons, Richard L.

AU - Ford, Henri

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Objective: To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. Design: Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43°C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, box, and bcl-2 expression was analyzed at various times by the Western blot method. Results: Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T- cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly upregulated box. The expression of p53 peaked at 4 hours and preceded maximal box induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased box levels. Levels of bcl-2 were unaffected. Conclusions: Our data show that lISP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and box expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.

AB - Objective: To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. Design: Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43°C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, box, and bcl-2 expression was analyzed at various times by the Western blot method. Results: Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T- cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly upregulated box. The expression of p53 peaked at 4 hours and preceded maximal box induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased box levels. Levels of bcl-2 were unaffected. Conclusions: Our data show that lISP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and box expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.

UR - http://www.scopus.com/inward/record.url?scp=0031453994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031453994&partnerID=8YFLogxK

U2 - 10.1001/archsurg.1997.01430360023004

DO - 10.1001/archsurg.1997.01430360023004

M3 - Article

C2 - 9403530

AN - SCOPUS:0031453994

VL - 132

SP - 1277

EP - 1282

JO - JAMA Surgery

JF - JAMA Surgery

SN - 2168-6254

IS - 12

ER -