PUBLICATION
Pyruvate plus uridine augment mitochondrial respiration and prevent cardiac hypertrophy in zebrafish and H9c2 cells
- Authors
- Mukherjee, S., Das, S., Das, S., Gupta, S., Hui, S.P., Sengupta, A., Ghosh, A.
- ID
- ZDB-PUB-250424-15
- Date
- 2025
- Source
- Journal of Cell Science : (Journal)
- Registered Authors
- Keywords
- Cardiomyocyte hypertrophy, Mitochondria, Phenylephrine, Respiration, Zebrafish
- MeSH Terms
-
- Pyruvic Acid*/pharmacology
- Reactive Oxygen Species/metabolism
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Myocytes, Cardiac/pathology
- Animals
- Cell Line
- Rats
- Phenylephrine/pharmacology
- Zebrafish
- Oxygen Consumption/drug effects
- Cell Respiration/drug effects
- Cardiomegaly*/metabolism
- Cardiomegaly*/pathology
- Cardiomegaly*/prevention & control
- Mitochondria*/drug effects
- Mitochondria*/metabolism
- Uridine*/pharmacology
- PubMed
- 40270134 Full text @ J. Cell Sci.
Citation
Mukherjee, S., Das, S., Das, S., Gupta, S., Hui, S.P., Sengupta, A., Ghosh, A. (2025) Pyruvate plus uridine augment mitochondrial respiration and prevent cardiac hypertrophy in zebrafish and H9c2 cells. Journal of Cell Science. :.
Abstract
Dysfunction of mitochondrial pyruvate oxidation and aberrant respiratory chain components are common in cardiac defects. However, the precise role of mitochondrial respiration in cardiomyocyte hypertrophy is unclear. Phenylephrine (PE) treatment on rat neonatal H9c2 cardiomyocytes promotes significant hypertrophy with decreased mitochondrial oxygen consumption rate (OCR), membrane potential, respiratory subunits NDUFB8, UQCRC2, and ATP5a expressions and accumulation of reactive oxygen species (ROS). Surprisingly, 60% reductions in cell survivability were observed in PE-treated cells compared to control cells grown under the respiratory-proficient galactose media. To revert H9c2 hypertrophy and survivability, we performed a screening with compounds that boost mitochondrial OCR and scavenge ROS, and identified pyruvate plus uridine as the best hit. Corroborated with the in vitro study, supplementation of pyruvate plus uridine significantly prevents PE-induced cardiac hypertrophy, pericardial edema, and bradycardia symptoms in zebrafish embryos. Moreover, pyruvate plus uridine decreases the ventricular and atrial area in cardiomyocyte-specific GFP transgenic Tg (myl7:HRAS-EGFP) lines. Using in vitro and in vivo models, we showed that boosting of mitochondrial respiration by pyruvate and scavenging ROS by uridine supplementations conjointly ameliorated cardiac hypertrophy and bradycardia symptoms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping