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dc.contributor.advisorGerner, Eugene W.en_US
dc.contributor.authorWIDELITZ, RANDALL BRUCE.
dc.creatorWIDELITZ, RANDALL BRUCE.en_US
dc.date.accessioned2011-10-31T16:51:38Z
dc.date.available2011-10-31T16:51:38Z
dc.date.issued1986en_US
dc.identifier.urihttp://hdl.handle.net/10150/183851
dc.description.abstractIn response to a variety of hyperthermic treatments, rat embryonic fibroblasts synthesize heat shock proteins (hsps), including those with molecular weights of 68,000 (hsp 68), 70,000 (hsp 70) and 89,000 (hsp 89). Hyperthermic stresses, which produce the hsps, also cause expression of thermotolerance. The dependence of thermotolerance expression on hsp synthesis was investigated in this mammalian cell line under different heating conditions. Temperature shift experiments showed that hsp synthesis and thermotolerance expression were dependent not only on the absolute hyperthermic temperature, but also on the difference between the initial incubation temperature and the hyperthermic temperature. Small temperature differences which produced no cell killing did not cause detectable synthesis of hsp 68. Increasing the difference of the initial and hyperthermic temperatures reduced cell survival and increased the synthesis of hsp 68. Thermotolerance could be expressed by surviving cells following an initial heat stress even when both heat shock and general protein synthesis were inhibited. Cells exposed to cycloheximide were heated, incubated at their initial temperature for six hours and reheated in the presence of the drug. The inhibitor was then removed and the cells plated for colony formation. The hsps were expressed during this latter incubation period. The regulation of hsp 70 in rat fibroblasts was investigated next. Hsp 70 synthesis rates correlated with the amount of hsp 70 encoding mRNA. The time course of heat shock synthesis and general protein synthesis recovery were each dependent on the duration of the heat stress. Inhibiting protein synthesis with cycloheximide resulted initially in the accumulation of the RNA encoding hsp 70 but did not effect the normal turnover of this RNA species. The conclusions based on these findings are that thermal survival adaptation can be expressed in the absence of hsp 68 synthesis. Hsp 68 is expressed by cells that will ultimately die (see Chapter 2). The hsps do not appear to protect cells against subsequent heat stress. They may function in a repair capacity (see Chapter 3). Hsp 70 expression is primarily regulated by transcription in Rat-1 cells. Hsp 70 does not act to regulate its own turnover (see Chapter 4).
dc.language.isoenen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectHeat -- Physiological effect.en_US
dc.subjectFibroblasts.en_US
dc.titleHEAT SHOCK PROTEIN SYNTHESIS AND THERMOTOLERANCE EXPRESSION IN RAT EMBRYONIC FIBROBLASTS (HYPERTHERMIA, GENE REGULATION).en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.identifier.oclc697637122en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.contributor.committeememberMagun, B. E.en_US
dc.contributor.committeememberDuffy, J.en_US
dc.contributor.committeememberBowden, G. T.en_US
dc.identifier.proquest8623838en_US
thesis.degree.disciplineMolecular and Medical Microbiologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.namePh.D.en_US
refterms.dateFOA2018-06-15T05:53:15Z
html.description.abstractIn response to a variety of hyperthermic treatments, rat embryonic fibroblasts synthesize heat shock proteins (hsps), including those with molecular weights of 68,000 (hsp 68), 70,000 (hsp 70) and 89,000 (hsp 89). Hyperthermic stresses, which produce the hsps, also cause expression of thermotolerance. The dependence of thermotolerance expression on hsp synthesis was investigated in this mammalian cell line under different heating conditions. Temperature shift experiments showed that hsp synthesis and thermotolerance expression were dependent not only on the absolute hyperthermic temperature, but also on the difference between the initial incubation temperature and the hyperthermic temperature. Small temperature differences which produced no cell killing did not cause detectable synthesis of hsp 68. Increasing the difference of the initial and hyperthermic temperatures reduced cell survival and increased the synthesis of hsp 68. Thermotolerance could be expressed by surviving cells following an initial heat stress even when both heat shock and general protein synthesis were inhibited. Cells exposed to cycloheximide were heated, incubated at their initial temperature for six hours and reheated in the presence of the drug. The inhibitor was then removed and the cells plated for colony formation. The hsps were expressed during this latter incubation period. The regulation of hsp 70 in rat fibroblasts was investigated next. Hsp 70 synthesis rates correlated with the amount of hsp 70 encoding mRNA. The time course of heat shock synthesis and general protein synthesis recovery were each dependent on the duration of the heat stress. Inhibiting protein synthesis with cycloheximide resulted initially in the accumulation of the RNA encoding hsp 70 but did not effect the normal turnover of this RNA species. The conclusions based on these findings are that thermal survival adaptation can be expressed in the absence of hsp 68 synthesis. Hsp 68 is expressed by cells that will ultimately die (see Chapter 2). The hsps do not appear to protect cells against subsequent heat stress. They may function in a repair capacity (see Chapter 3). Hsp 70 expression is primarily regulated by transcription in Rat-1 cells. Hsp 70 does not act to regulate its own turnover (see Chapter 4).


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