S100A10 knockdown exacerbates phenylephrine-induced cardiomyocyte hypertrophy via modulating mitochondrial oxidative...

Area of Science:

• Cardiology
• Molecular Biology
• Mitochondrial Biology

Background:

• Mitochondrial dysfunction is a key feature of cardiac hypertrophy.
• S100A10, a calcium-binding protein, influences mTOR signaling and mitochondrial function.
• The precise role of S100A10 in phenylephrine-induced cardiomyocyte hypertrophy requires elucidation.

Purpose of the Study:

• To investigate the role of S100A10 in phenylephrine (PE)-induced cardiomyocyte hypertrophy.
• To explore the mechanistic basis of S100A10's function in this context.
• To determine S100A10's impact on mitochondrial function and mTOR signaling.

Main Methods:

• Phenylephrine (PE) was used to induce hypertrophy in primary neonatal rat cardiomyocytes (NRCMs).
• S100A10 was downregulated using siRNA, and its interaction with ANXA2 was assessed via co-immunoprecipitation.
• Western blotting analyzed mTOR pathway activation; mitochondrial function was evaluated through electron transport chain complex expression, mitochondrial membrane potential (JC-1), and oxidative stress (MitoSOX).

Main Results:

• S100A10 expression was elevated in hypertrophic murine hearts.
• S100A10 was found to interact with ANXA2, activating the mTOR/4E-BP signaling pathway.
• S100A10 knockdown in NRCMs led to reduced mitochondrial respiratory chain proteins, impaired oxidative phosphorylation, decreased mitochondrial membrane potential, and lower ATP production.

Conclusions:

• Downregulation of S100A10 exacerbates PE-induced cardiomyocyte hypertrophy.
• S100A10 plays a novel role in regulating mitochondrial respiratory chain protein levels, potentially via the mTOR/4E-BP pathway.
• These findings offer a potential theoretical basis for developing new therapeutic strategies for cardiac hypertrophy.