Overexpression of Wild-Type Heat Shock Protein 27 and a Nonphosphorylatable Heat Shock Protein 27 Mutant Protects Against Ischemia/Reperfusion Injury in a Transgenic Mouse Model

Publisher Website
Google Scholar
Abstract
Background— The small heat shock protein 27 (hsp27) increases in expression with ischemia/reperfusion (I/R) insult in the heart. One feature of the small hsps is their ability to oligomerize and form intracellular aggregates. Oligomerization pattern is governed by the phosphorylation state of the protein that may influence their ability to protect against cellular stresses. Methods and Results— We generated transgenic (tg) mice that overexpress a wild-type human hsp27 (hsp27tg) protein or a mutant hsp27 protein (mut-hsp27tg), in which serine residues (aa15, aa78, and aa82) were replaced by alanine residues, rendering them incapable of phosphorylation. Using a Langendorff perfusion model and an intraventricular balloon, we subjected hearts to 20 minutes of ischemia followed by 1 hour of reperfusion. During reperfusion, negative and positive pressure derivatives as well as developed pressures were significantly higher in both hsp27tg and mut-hsp27tg compared with control (PPPConclusions— These results indicate that in a tg mouse model, overexpression of either wild-type hsp27 or a nonphosphorylatable hsp27 mutant was equally capable of protecting the heart from I/R injury. Furthermore, the phosphorylation status of hsp27 may influence its ability to decrease oxidative stress.

This publication has 35 references indexed in Scilit: