THE ROLE OF YAP SIGNALLING IN STRESSORS ASSOCIATED WITH MYOCARDIAL INFARCTION

Abstract

Due to myocardial infarction (MI) a loss of viable cardiomyocytes significantly reduces cardiac function and patients’ quality of life. This loss is caused partly by definitive stressors as a result of ischemia. The Yap signalling pathway is a regulator of fetal heart development—its role in adult cardiomyocytes after MI remains to be defined. Using differentiated rat cardiomyotubules (H9c2) we independently screened stressors associated with ischemia as: hypoxia, oxidative stress, inflammation, autophagy, and nutrient deprivation. We found Yap was most sensitive to nutrient deprivation. We then created a nutrient deprivation model as media deprived of the nutrient substrates. Our data suggest that the translocation of phosphorylated Yap is affected under this metabolic stress. Additionally, we found isoleucine could play an important role in cytoplasmic retention of phospho-Yap S397 and contributes to the upregulation of structural integrity-related genes.