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Effect of methylglyoxal modification and phosphorylation on the chaperone and anti-apoptotic properties of heat shock protein 27.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2006 Sep 01; Vol. 99 (1), pp. 279-91. - Publication Year :
- 2006
-
Abstract
- Heat shock protein 27 (Hsp27) is a stress-inducible protein in cells that functions as a molecular chaperone and also as an anti-apoptotic protein. Methylglyoxal (MGO) is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts non-enzymatically with proteins to form products such as argpyrimidine. We found considerable amount of Hsp27 in phosphorylated form (pHsp27) in human cataractous lenses. pHsp27 was the major argpyrimidine-modified protein in brunescent cataractous lenses. Modification by MGO enhanced the chaperone function of both pHsp27 and native Hsp27, but the effect on Hsp27 was at least three-times greater than on pHsp27. Phosphorylation of Hsp27 abolished its chaperone function. Transfer of Hsp27 using a cationic lipid inhibited staurosporine (SP)-induced apoptotic cell death by 53% in a human lens epithelial cell line (HLE B-3). MGO-modified Hsp27 had an even greater effect (62% inhibition). SP-induced reactive oxygen species in HLE-B3 cells was significantly lower in cells transferred with MGO-modified Hsp27 when compared to native Hsp27. In vitro incubation experiments showed that MGO-modified Hsp27 reduced the activity of caspase-9, and MGO-modified pHsp27 reduced activities of both caspase-9 and caspase-3. Based on these results, we propose that Hsp27 becomes a better anti-apoptotic protein after modification by MGO, which may be due to multiple mechanisms that include enhancement of chaperone function, reduction in oxidative stress, and inhibition of activity of caspases. Our results suggest that MGO modification and phosphorylation of Hsp27 may have important consequences for lens transparency and cataract development.
- Subjects :
- Age Factors
Aged
Animals
Apoptosis Regulatory Proteins chemistry
Apoptosis Regulatory Proteins pharmacology
Caspase 3
Caspase 9
Caspases metabolism
Cattle
Cells, Cultured
Citrate (si)-Synthase metabolism
Epithelial Cells drug effects
Epithelial Cells metabolism
Heat-Shock Proteins chemistry
Heat-Shock Proteins pharmacology
Humans
Lens, Crystalline cytology
Molecular Chaperones chemistry
Phosphorylation
Pyruvaldehyde chemistry
Reactive Oxygen Species metabolism
alpha-Crystallins metabolism
Apoptosis Regulatory Proteins metabolism
Cataract metabolism
Heat-Shock Proteins metabolism
Lens, Crystalline metabolism
Molecular Chaperones metabolism
Pyruvaldehyde metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 99
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16615138
- Full Text :
- https://doi.org/10.1002/jcb.20781