Heart Shock Protein Beta-1 Promotes Doxorubicin-Induced Hl-1 Cardiomyocyte Pyroptosis By Inhibiting Apoptosis Antagonizing Transcription Factor

Author(s): Yao Tang, Yaxiu Liu, Hui Fu, Shuang Fu, Xinbin Zheng and Deling Yin

Doxorubicin (DOX) is a treatment for many types of cancer that works well. Long-term use of DOX is limited because of possible risks, such as cardiotoxicity. A lot of research has been done on the ways in which DOX causes cardiotoxicity, but more research is still needed. The role of heat shock proteins (HSPs) in apoptosis and pyroptosis in cells has just been discovered. Doxorubicin makes cardiomyocytes go through pyroptosis, but it is not known if heat shock protein beta-1 (HSPB1), a member of the HSPs family, plays a role in this process. We looked at the effects of apoptosis antagonizing transcription factor (AATF) and heat shock protein beta-1 (HSPB1) on HL-1 cardiomyocyte pyroptosis caused by 5 μM DOX for 9 hours. When cardiomyocytes are treated with DOX, HSPB1 levels go up a lot while AATF levels go down a lot. When HSPB1 was turned off or AATF was turned up, it inhibited DOX from causing pyroptosis in cardiomyocytes. There is a chance that stopping HSPB1, raising AATF, or both could make DOX less harmful to the heart. Our results show that the HSPB1-AATF-caspase-3-GSDME pathway controls cardiomyocyte pyroptosis in response to DOX treatment in a way that wasn't known before. This suggests that HSPB1-AATF-dependent pyroptosis may be a good way to treat DOX-induced cardiotoxicity.