Cytotoxicity and cell signalling induced by continuous mild hyperthermia in freshly isolated mouse hepatocytes.
An increasing body of data has been demonstrating that mammalian cells have elaborate networks of molecular signalling in counteracting heat shock and in developing adaptation to oxidative stress to avoid cell death. However, the precise mechanisms linking heat shock, oxidative stress and cell survival/cell death mechanisms are not yet clearly understood. The purpose of this study was thus to study the time course of hyperthermia-induced oxidative stress and cellular signalling through the activation of heat shock factor 1 (HSF1) and heat shock protein 70 (HSP70), using freshly isolated mouse hepatocytes. The results accomplished in this work demonstrated that mild continuous hyperthermia (41 degrees ) leads to oxidative stress and loss of cellular viability in a time-dependent manner, with significant effects already observed at the first hour of incubation. These toxic effects developed concomitantly with activation of HSF1 and emerged before the formation of HSP70 levels. Thus, although cell signalling was triggered through the transcriptional activation of HSP70 via HSF1, this putative protective process did not modify the trend of hepatotoxic effects mediated by this type of hyperthermic challenging.
Santos-Marques
Maria João
MJ
REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal. mjsantosmarques@hotmail.com
Carvalho
Félix
F
Sousa
Carla
C
Remião
Fernando
F
Vitorino
Rui
R
Amado
Francisco
F
Ferreira
Rita
R
Duarte
José Alberto
JA
de Lourdes Bastos
Maria
M
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006358:Hot Temperature; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D017392:Thiobarbituric Acid Reactive Substances; D014157:Transcription Factors; D005978:Glutathione; D019803:Glutathione Disulfide