허혈성 심질환 치료용 융합단백질 개발

Abstract

Ischemia heart disease has drawn a lot of attention for being one of the largest globalize killer. Thus, many researchers intended to cure this disease by searching and investigating to discover new therapeutic products to overcome this problem. Hsp27 overexpression has been shown in many cases where heart muscle cells undergo ischemia/reperfusion conditions. Furthermore, the function of Hsp27 was revealed as it can bind to several apoptosis components to carry out its role as an anti-apoptosis protein. From the hypoxia condition for H9c2, PTD-Hsp27 were able to decrease 30% of apoptotic cells while there were more significant results shown in the primary myocyte cells where the reduction of apoptotic cells was about 40% compared to control. PTD-Hsp27 fusion proteins were also proved to be effective in protecting cells undergo apoptosis induced by either the extrinsic or intrinsic pathway. In the intrinsic apoptosis pathway tested with staurosporine, 34% and 67% of reduction in caspase-3 activity compared to control was shown after the treatment with Tat-Hsp27 and 11R-Hsp27 respectively. Intriguingly, Tat-Hsp27 and 11R-Hsp27 significantly reduced apoptotic cells in the hypoxia mimicking agent, cobalt chloride induced extrinsic pathway up to 52% and 76% respectively. Therefore, it was proved that the PTD-Hsp27 was more effective in interrupting at the extrinsic apoptosis pathway. Overall, this research demonstrated promising results for the treatment of ischemia heart disease with the treatment of PTD-Hsp27.