Document Detail


Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes.
MedLine Citation:
PMID:  16950797     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.
Authors:
Cecilia Bivik; Inger Rosdahl; Karin Ollinger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-31
Journal Detail:
Title:  Carcinogenesis     Volume:  28     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-21     Completed Date:  2007-09-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  537-44     Citation Subset:  IM    
Affiliation:
Division of Dermatology, Department of Biomedicine and Surgery, Linköping University, Linköping, Sweden. cecbi@ibk.liu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / radiation effects*
Caspases / metabolism,  radiation effects
Cathepsins / metabolism*,  radiation effects
Cytochromes c / metabolism*
Enzyme Activation
HSP70 Heat-Shock Proteins / physiology*
Hot Temperature
Humans
Intracellular Membranes / physiology,  radiation effects
Liver / physiology
Lysosomes / physiology,  radiation effects
Melanocytes / physiology*,  radiation effects
Mitochondria / radiation effects
Mitochondria, Liver / physiology
Rats
Recombinant Proteins / metabolism
Skin / radiation effects
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/Recombinant Proteins; 9007-43-6/Cytochromes c; EC 3.4.-/Cathepsins; EC 3.4.22.-/Caspases

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