Dual effects of heat stress on tumor necrosis factor-α-induced hepatocyte apoptosis in mice
| Autor: | Motohiro Imao, Masahito Nagaki, Hisataka Moriwaki |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Programmed cell death medicine.medical_specialty Hot Temperature Time Factors CASP8 and FADD-Like Apoptosis Regulating Protein Apoptosis Biology Heat Stress Disorders Caspase 8 Pathology and Forensic Medicine Mice Downregulation and upregulation Internal medicine Heat shock protein medicine Animals HSP70 Heat-Shock Proteins Molecular Biology Liver injury Mice Inbred BALB C Tumor Necrosis Factor-alpha Intracellular Signaling Peptides and Proteins Cell Biology medicine.disease Hsp70 medicine.anatomical_structure Endocrinology Liver Caspases Hepatocyte Immunology Hepatocytes Proto-Oncogene Proteins c-akt |
| Zdroj: | Laboratory Investigation. 86:959-967 |
| ISSN: | 0023-6837 |
| Popis: | The major heat shock protein, HSP70, plays a critical role in cell survival in response to stress, possibly by inhibiting a number of antisurvival pathways. However, heat stress (HS) and HSPs also sensitize cells to certain apoptotic stimuli, such as TNF-alpha. To clarify the relations between HS and apoptosis, we examined the differential effects of the intensity of HS on liver injury and apoptosis induced by TNF-alpha in mice. TNF-alpha was injected into D-galactosamine (GalN)-sensitized mice that were pretreated with or without HS. Liver injury was assessed biochemically and histologically. In GalN-sensitized mice, application of HS for 7 days led to significant enhancement of TNF-alpha-induced hepatotoxicity, despite upregulation of HSP70 in the liver. In contrast, application of HS for 1 day led to attenuation of TNF-alpha-induced liver injury. Repeated HS decreased the levels of the FLICE inhibitory protein short (FLIP(S)) and activated caspase-8 in the liver. The caspase-8 inhibitor Z-IETD-FMK effectively protected both the nontreated and HS-pretreated mice from the hepatotoxicity induced by GalN/TNF-alpha. HS shows dual effects on TNF-alpha-induced hepatocyte apoptosis. Exposure to repeated HS, but not to single HS, leads to enhancement of TNF-alpha-induced hepatocyte apoptosis via the interaction of FLIP and caspase-8. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|