CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and apoptosis by promoting NFATc3 proteasomal degradation

Chun Nun Chao, Chao Hung Lai, Khan Farheen Badrealam, Jeng Fan Lo, Chia Yao Shen, Chia Hua Chen, Ray Jade Chen, Vijaya Padma Viswanadha, Wei Wen Kuo, Chih Yang Huang

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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.

Original languageEnglish
Pages (from-to)20128-20138
Number of pages11
JournalJournal of Cellular Physiology
Volume234
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

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Keywords

  • apoptosis
  • CHIP
  • hypertrophy
  • lipopolysaccharide
  • NFATc3

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Chao, C. N., Lai, C. H., Badrealam, K. F., Lo, J. F., Shen, C. Y., Chen, C. H., Chen, R. J., Viswanadha, V. P., Kuo, W. W., & Huang, C. Y. (2019). CHIP attenuates lipopolysaccharide-induced cardiac hypertrophy and apoptosis by promoting NFATc3 proteasomal degradation. Journal of Cellular Physiology, 234(11), 20128-20138. https://doi.org/10.1002/jcp.28614