Small Heat Shock Proteins and Doxorubicin-Induced Oxidative Stress in the Heart

摘要: Doxorubicin (Dox) and its derivatives are used as chemotherapeutics, either alone or in combination with other agents. Dilated cardiomyopathy congestive heart failure due to cardiotoxicity continues be the most serious side effect, imposing severe limitations use of these agents despite arrival new classes Dox-derivatives formulations. In this chapter we summarize recent understanding mechanism Dox-induced relevance stress-inducible proteins, special emphasis on small heat shock proteins such Hsp27, Hsp20, etc. The expressed a response oxidative stress redox reactions drugs generation reactive oxygen species (ROS). On hand, ROS also known induce various MAP kinases phosphorylate activate stress-responding transcription factors, including factors (HSF). Activation HSF-1 leads induction series depending upon type exerted stress. Recent studies have confirmed that indeed activation especially Hsps heart. been found involved cell signaling can cardioprotective detrimental. Additionally, few transgenic animal models shown selective overexpression against Dox. These results establish fact proper regulation function could eliminate serve potential therapeutic target protect from toxicity.