| Affiliation: | 1. Department of Biotechnology, Asia University, Taichung, Taiwan Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan;2. Division of Cardiology, Department of Internal Medicine, Armed Force Taichung, General Hospital, Taichung, Taiwan;3. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;4. Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan;5. Department of Nursing, MeiHo University, Pingtung, Taiwan;6. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;7. Department of Biotechnology, Bharathiar University, Coimbatore, India;8. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;9. Department of Biotechnology, Asia University, Taichung, Taiwan |
| Abstract: | Carboxyl-terminus of Hsc70 interacting protein (CHIP) is a chaperone-dependent E3-ubiquitin ligase with important function in protein quality control system. In the current research endeavor, we have investigated the putative role of CHIP in lipopolysaccharides (LPS)-induced cardiomyopathies. Basically, H9c2 cardiomyoblasts were transfected with CHIP for 24 hr, and thereafter, treated with LPS for 12 hr. Concomitantly, western blot analysis, actin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and coimmunoprecipitation studies were performed to investigate the underlying intricacies. Interestingly, western blot analysis revealed that the expression of hypertrophy and apoptosis-related proteins were considerably reduced following overexpression of CHIP. Moreover, Actin staining and TUNEL assay further ascertained the attenuation of cardiac hypertrophy and apoptosis following overexpression of CHIP respectively. These aspects instigate the role of CHIP in attenuation of LPS-induced cardiomyopathies. Additionally and importantly, co-immunoprecipitation and western blot studies revealed that CHIP plausibly promotes degradation of nuclear factor of activated T cells 3 (NFATc3) through ubiquitin-proteasomal pathway. Taken together, our study reveals that CHIP attenuates LPS-induced cardiac hypertrophy and apoptosis perhaps by promoting NFATc3 proteasomal degradation. |
