The Role Played by TFE3 Protein in Cardiac Function and Disease - The 65th Annual Conference of the Israel Heart Society & The Israel Society of Cardiothoracic Surgery, 24-25 April 2018

Ahmed Rishiq Biochemistry and Molecular Biology, Hebrew University-School of Medicine-IMRIC, Jerusalem, Jerusalem, Israel Sagi Tshori Biochemistry and Molecular Biology, Hebrew University-School of Medicine-IMRIC, Jerusalem, Jerusalem, Israel Dan Gilon Biochemistry and Molecular Biology, Hebrew University-School of Medicine-IMRIC, Jerusalem, Jerusalem, Israel Cardiology, Hadassah medical center, Jerusalem, Jerusalem, Israel Roger Foo Heart Center, National University of Singapore, Singapore, Singapore, Singapore Ehud Razin Biochemistry and Molecular Biology, Hebrew University-School of Medicine-IMRIC, Jerusalem, Jerusalem, Israel

TFE3 is a basic helix-loop-helix leucine zipper (bHLH-Zip) DNA-binding protein. This protein plays a predominant role in osteoclast development, mast cell function and renal cell carcinoma. Furthermore, TFE3 has been shown to be involved in autophagy and stress response in a human retinal pigment epithelial cell line. The role played by TFE3 in cardiac function has not yet been studied. In our work we observed by using mass spectrometry assay from whole heart lysates as well as rat cardiomyoblasts cell line (H9c2) the specific interactions between TFE3 and four of the aminoacyl tRNA synthetase complex (MSC) proteins. This interaction has been verified using co-immunoprecipitation as well as by size exclusion chromatography. In the latter assay, TFE3 was shown to be located in the same elution fraction of the MSC which would indicate the coexistence of TFE3-MSC interaction. Moreover, TFE3^-/-mice as well as their normal littermates were injected with 15 mg/kg isoproterenol IP once daily for 8 days and echocardiography was performed both at baseline and at day 8. Interestingly, we found that heart weight to body weight(HW/BW) ratio was increased by 18% in wild type mice, only a 7% increase was observed in TFE3^-/-mice siblings (n=6-8, p=0.0174). However, there was no significant change in shortening fraction or LV diameters between all groups. Thus, based on our preliminary data it seems that there is a diminished response to beta agonist hypertrophic stimulus in TFE3^-/-mice, but whether the diminished response in detrimental or beneficial is yet to be determined.