Cytotoxicity and cell signalling induced by continuous mild hyperthermia in freshly isolated mouse hepatocytes
- 作者：Maria Joã ; o Santos-Marques ; Fé ; lix Carvalho ; Carla Sousa ; Fernando Remiã ; o ; Rui Vitorino ; Francisco Amado ; Rita Ferreira ; José ; Alberto Duarte and Maria de Lourdes Bastos
- 关键词：Hyperthermia ; Mouse hepatocytes ; Oxidative stress ; Heat shock ; Cell signalling
- 刊名：Toxicology
- 出版年：2006
- 期刊代码：47_0300483x
- 类别：pha
- 出版时间：25 July 2006
- 卷：224
- 期：3
- 页码：210-218
- 文件大小：286 K
摘要
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°) 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.