Assuntos
Anticorpos Antibacterianos/uso terapêutico , Planejamento em Desastres , Lipopolissacarídeos/imunologia , Guerra Nuclear , Lesões por Radiação/terapia , Choque Séptico/prevenção & controle , Humanos , Lesões por Radiação/complicações , Lesões por Radiação/fisiopatologia , Choque Séptico/etiologia , Choque Séptico/fisiopatologiaRESUMO
We studied the effect of heat shock on gene expression by normal human cells. Peripheral blood mononuclear cells (PBMCs) were obtained from healthy adults. Paired samples from each subject were subjected to either 20 min of heat shock (43 degrees C) or control (37 degrees C) conditions and then returned to 37 degrees C. RNA was isolated 160 min later, and five representative samples were analyzed on Affymetrix gene chip arrays containing approximately 12,600 probes. A biologically meaningful effect was defined as a statistically significant, twofold or greater difference in expression of sequences that were detected in all five experiments under control (downregulated sequences) or heat shock (upregulated sequences) conditions. Changes occurred in 395 sequences (227 increased by heat shock, 168 decreased), representing 353 Unigene numbers, in every functional category previously implicated in the heat shock response. By RT-PCR, we confirmed the findings for one upregulated sequence (Rad, a G protein) and one downregulated sequence (osteopontin, a cytokine). We conclude that heat shock causes extensive gene expression changes in PBMCs, affecting all functional categories of the heat shock response.
Assuntos
Perfilação da Expressão Gênica , Proteínas de Choque Térmico , Resposta ao Choque Térmico/fisiologia , Leucócitos Mononucleares/metabolismo , Adulto , Chaperoninas/genética , Chaperoninas/metabolismo , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico/genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Osteopontina , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Regulação para Cima , Proteínas ras/genética , Proteínas ras/metabolismoRESUMO
This review examines the effects of thermal stress on gene expression, with special emphasis on changes in the expression of genes other than heat shock proteins (HSPs). There are approximately 50 genes not traditionally considered to be HSPs that have been shown, by conventional techniques, to change expression as a result of heat stress, and there are <20 genes (including HSPs) that have been shown to be affected by cold. These numbers will likely become much larger as gene chip array and proteomic technologies are applied to the study of the cell stress response. Several mechanisms have been identified by which gene expression may be altered by heat and cold stress. The similarities and differences between the cellular responses to heat and cold may yield key insights into how cells, and by extension tissues and organisms, survive and adapt to stress.
