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.

The effects of radiofrequency electromagnetic radiation on sperm function

“…As both of these pathways are known to be redox regulated, it is possible that RF-EMR activates these signal transduction cascades as a secondary consequence of ROS production (Christman et al 1985, Polla et al 1996, Nahomi et al 2015. As indicated previously, the major site of intracellular ROS generation observed after RF-EMR exposure is the mitochondria.…”

Expression and localization of the Xenopus laevis small heat shock protein, HSPB6 (HSP20), in A6 kidney epithelial cells

“…This latter study and others have shown that HSPB6 was not upregulated by heat shock although enhanced levels of this sHSP were detected in cells or tissues subjected to other stressors that function via other signalling pathways (Kato et al, 1994;Marvin et al, 2008;Kirbach and Golenhofen, 2011;Edwards et al, 2011;Mymrikov et al, 2011). HSPB6 was reported to function as an ATP-independent molecular chaperone since it was able to inhibit either heat-or chemical-induced aggregation of various client proteins (Van de Klundert et al, 1998;Bukach et al, 2004;Heirbaut et al, 2014;Nahomi et al, 2015). Furthermore, the interaction of HSPB6 with various protein kinases and its phosphorylation appears to be important in its roles in muscle contraction, cardioprotection, and insulin resistance (Fan et al, 2005;Dreiza et al, 2010;Edwards et al, 2011;Mymrikov et al, 2011).…”

“…Furthermore, the interaction of HSPB6 with various protein kinases and its phosphorylation appears to be important in its roles in muscle contraction, cardioprotection, and insulin resistance (Fan et al, 2005;Dreiza et al, 2010;Edwards et al, 2011;Mymrikov et al, 2011). Other roles proposed for HSPB6 include the regulation of platelet function as well as the acquisition of thermotolerance and anti-apoptotic activity (Myrmikov et al, 2011;Nagasawa et al, 2014;Nahomi et al, 2015).…”

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

“…In addition to its established role in sHSPs oligomerization, the hydrophobic groove in HSPB6 links the sHSPs to the degradation of [48]. Moreover, depletion of Bag3 also abrogated the chaperone activity HSPB6 towards the aggregation-prone protein HttQ43, indicating that HSPB6 is strictly dependent upon its binding to Bag3 to stimulate Htt43Q clearance [48] Recently, peptides from HSPB6 and the HSPB1, with sequence homology to HSPB5, were demonstrated as molecular chaperones [49]. HSPB6 and HSPB1 peptides, despite performing better chaperone activities than the HSPB5 peptide, had the same degree of surface hydrophobicity as the HSPB5 peptide [49].…”

“…Moreover, depletion of Bag3 also abrogated the chaperone activity HSPB6 towards the aggregation-prone protein HttQ43, indicating that HSPB6 is strictly dependent upon its binding to Bag3 to stimulate Htt43Q clearance [48] Recently, peptides from HSPB6 and the HSPB1, with sequence homology to HSPB5, were demonstrated as molecular chaperones [49]. HSPB6 and HSPB1 peptides, despite performing better chaperone activities than the HSPB5 peptide, had the same degree of surface hydrophobicity as the HSPB5 peptide [49]. Such a disconnect between surface hydrophobicity and chaperone activity, thus, suggested that the hydrophobic surface of sHSP is not the sole determining factor for the chaperone activity.…”