Publications
Detailed Information
HSP70 deficiency results in activation of c-Jun N-terminal Kinase, extracellular signal-regulated kinase, and caspase-3 in hyperosmolarity-induced apoptosis
Cited 92 time in
Web of Science
Cited 90 time in Scopus
- Authors
- Issue Date
- 2004-12-14
- Citation
- J Biol Chem. 2005 Feb 25;280(8):6634-41. Epub 2004 Dec 7.
- Keywords
- Animals ; Caspase 3 ; Caspases/antagonists & inhibitors/*metabolism ; Cells, Cultured ; Dual Specificity Phosphatase 1 ; Embryo, Mammalian/cytology ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; HSP70 Heat-Shock Proteins/deficiency/genetics/*physiology ; JNK Mitogen-Activated Protein Kinases/*metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Phosphorylation ; Protein Phosphatase 1 ; Protein Tyrosine Phosphatases/metabolism ; Transfection ; Apoptosis ; Osmotic Pressure
- Abstract
- In this study we examined the function of heat shock protein 70 (HSP70) in the hyperosmolarity-induced apoptotic pathway using hsp70.1-/-mouse embryonic fibroblasts (MEFs). When the cells were exposed to hyperosmotic stress, an absence of HSP70 negatively affected cell viability. Caspase-9 and caspase-3 were rapidly activated, and extensive cleavage occurred in focal adhesion and cytoskeletal molecules in the hsp70.1-/-MEFs. In contrast, hsp70.1+/+ MEFs exhibited no caspase-9 or caspase-3 activation and finally recovered intact cell morphology when cells were shifted back to an isosmotic state. Because HSP70 might be involved in the regulation of mitogen-activated protein kinase (MAPK) activities with regard to various cellular activities, we also monitored MAPK phosphorylation. The absence of HSP70 affected c-Jun N-terminal kinase phosphorylation. However, it had no effect on p38. Sustained phosphorylation of extracellular signal-regulated kinase (ERK) was observed during the hyperosmolarity-induced apoptosis of hsp70.1-/-MEFs. Inhibition of ERK activity by the treatment of PD98059 accelerated the apoptotic pathway. ERK phosphorylation was precisely correlated with shift of mitogen-activated protein kinase phosphatase-3 from the soluble to insoluble fraction. Our results demonstrate that the inhibitory effect of HSP70 on caspase-3 activation is sufficient to inhibit apoptosis and that HSP70 exhibits regulatory functions to c-Jun N-terminal kinase and ERK phosphorylation in hyperosmolarity-induced apoptosis.
- ISSN
- 0021-9258 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15590690
https://hdl.handle.net/10371/29642
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.