title: Identification of peptides in human Hsp20 and Hsp27 that possess molecular chaperone and anti-apoptotic activities.
abstract: Previous studies have identified peptides in the 'crystallin-domain' of the small heat-shock protein (sHSP) α-crystallin with chaperone and anti-apoptotic activities. We found that peptides in heat-shock protein Hsp20 (G71HFSVLLDVKHFSPEEIAVK91) and Hsp27 (D93RWRVSLDVNHFAPDELTVK113) with sequence homology to α-crystallin also have robust chaperone and anti-apoptotic activities. Both peptides inhibited hyperthermic and chemically induced aggregation of client proteins. The scrambled peptides of Hsp20 and Hsp27 showed no such effects. The chaperone activities of the peptides were better than those from αA- and αB-crystallin. HeLa cells took up the FITC-conjugated Hsp20 peptide and, when the cells were thermally stressed, the peptide was translocated from the cytoplasm to the nucleus. The two peptides inhibited apoptosis in HeLa cells by blocking cytochrome c release from the mitochondria and caspase-3 activation. We found that scrambling the last four amino acids in the two peptides (KAIV in Hsp20 and KTLV in Hsp27) made them unable to enter cells and ineffective against stress-induced apoptosis. Intraperitoneal injection of the peptides prevented sodium-selenite-induced cataract formation in rats by inhibiting protein aggregation and oxidative stress. Our study has identified peptides from Hsp20 and Hsp27 that may have therapeutic benefit in diseases where protein aggregation and apoptosis are contributing factors.
authors.affiliation: *Department of Ophthalmology & Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A.
authors.forename: Rooban B
authors.initials: RB
authors.lastname: Nahomi
authors.affiliation: *Department of Ophthalmology & Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A.
authors.forename: Michael A
authors.initials: MA
authors.lastname: DiMauro
authors.affiliation: †Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A.
authors.forename: Benlian
authors.initials: B
authors.lastname: Wang
authors.affiliation: *Department of Ophthalmology & Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, U.S.A.
authors.forename: Ram H
authors.initials: RH
authors.lastname: Nagaraj
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002386:Cataract / Q000188:drug therapy; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D050886:HSP20 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D020887:Selenious Acid; D013312:Stress, Physiological / Q000187:drug effects; D013329:Structure-Activity Relationship; D038201:alpha-Crystallins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D050886:HSP20 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; C494382:HSPB6 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010455:Peptides; D066329:Protein Aggregates; D038201:alpha-Crystallins; D020887:Selenious Acid