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The pseudoenzyme ADPRHL1 affects cardiac function by regulating the ROCK pathway.

Lei Tian1,2, Tianwei Guo3, Fujian Wu4,5

  • 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.

Stem Cell Research & Therapy
|October 26, 2023
PubMed
Summary

ADP-ribosylhydrolase-like 1 (ADPRHL1) pseudoenzyme is crucial for cardiomyocyte function. Its absence disrupts heart cell adhesion and electrical activity by upregulating the ROCK-myosin II pathway, suggesting therapeutic potential.

Keywords:
ADPRHL1CRISPR/cas9Focal adhesionsROCK pathway

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Area of Science:

  • Cardiology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Pseudoenzymes, catalytically impaired enzymes, regulate cellular processes.
  • ADP-ribosylhydrolase-like 1 (ADPRHL1) is a pseudoenzyme implicated in heart development, but its specific role is unknown.
  • This study addresses the function of ADPRHL1 in cardiac development using a novel human embryonic stem cell model.

Purpose of the Study:

  • To investigate the role of ADP-ribosylhydrolase-like 1 (ADPRHL1) in human cardiomyocyte function.
  • To elucidate the molecular mechanisms underlying ADPRHL1's function in the heart.

Main Methods:

  • Generated ADPRHL1 knockout human embryonic stem cells (hESCs) using CRISPR/Cas9.
  • Differentiated hESCs into cardiomyocytes and assessed calcium transients and electrophysiological activity.
  • Utilized Bulk RNA sequencing and Western blot to explore cellular mechanisms.

Main Results:

  • ADPRHL1 deficiency in cardiomyocytes caused abnormal adhesion and disrupted calcium transients and electrical activity.
  • Focal adhesion formation was impaired due to ROCK-myosin II pathway upregulation.
  • Inhibiting ROCK and myosin II restored focal adhesions and improved cardiomyocyte function.

Conclusions:

  • ADPRHL1 is essential for normal cardiomyocyte function by regulating the ROCK-myosin II pathway.
  • ADPRHL1's role in cardiac development and function presents a potential therapeutic target for related diseases.