ABUNDANCE AND LOCATION OF THE SMALL HEAT-SHOCK PROTEINS HSP25 AND ALPHA-B-CRYSTALLIN IN RAT AND HUMAN HEART

Background in the heart, there are high constitutive levels of the two related small heat shock proteins, HSP25 and alpha B-crystallin. To g ain insight into their functional role, we have analyzed abundance and location of both proteins in rat and human hearts at different stages of development and in diseased state. Methods and Results Immunoblott ing analysis of rat ventricular tissue at fetal, neonatal, and adult s tages reveals the level of HSP25 to decline strongly during developmen t, whereas the level of alpha B-crystallin remains nearly constant. In parallel, the portion of phosphorylated isoforms of HSP25 decreases a s shown by two-dimensional polyacrylamide gel electrophoresis, HSP25 i s detected in cardiomyocytes and endothelial and vascular smooth muscl e cells, whereas alpha B-crystallin is detected in cardiomyocytes only by immunofluorescence and immunoelectron microscopy. Both proteins co localize in the I-band and M-line region of myofibrils in cardiomyocyt es. In diseased and transplanted adult human hearts, HSP25 and alpha B -crystallin levels are considerably elevated compared with fetal heart s, In failing adult human hearts, phosphorylated isoforms of HSP25 pre dominate, and cardiomyocytes with a partial dislocation of HSP25 and a lpha B-crystallin are observed. Conclusions Differential accumulation and location of HSP25 and alpha B-crystallin in heart tissue during de velopment imply distinct functions of both proteins, which seem to be involved in organization of cytoskeletal structures. As judged by leve l, phosphorylation state, and location of both small heat shock protei ns, diseased adult human hearts share features with fetal hearts.