# Proteomic Profiling of Cardiomyocytes Revealed Potential Radioprotective Effects of Different Resveratrol Pretreatment Regimens

## TL;DR

This study shows that long-term resveratrol pretreatment can protect heart cells from radiation damage by altering their protein profiles.

## Contribution

The study reveals time-dependent cardioprotective effects of resveratrol through proteomic reprogramming in cardiomyocytes.

## Key findings

- Extended resveratrol treatment increased cell survival and reduced cell death and G1 arrest after radiation.
- Three distinct protein subsets were identified, showing different responses to radiation depending on resveratrol pretreatment duration.
- Long-term resveratrol pretreatment induced proteomic changes linked to metabolism regulation and DNA repair.

## Abstract

Resveratrol may protect against radiation by modulating cellular metabolism and enhancing the cellular response to stress. Here, we explored its effects on human cardiomyocytes exposed to ionizing radiation. Resveratrol (5 µM) was administered for 1, 7, and 30 days before a single 2 Gy dose of irradiation, and then radiation toxicity and changes in the proteome were evaluated. Extended resveratrol treatment (7 or 30 days) induced more profound proteomic changes than one-day treatment and partially counteracted toxic effects of radiation, leading to increased cell survival, reduced cell death, and fewer cells arrested in the G1 phase. Though resveratrol administration itself had a greater impact on the proteome than radiation alone, we identified three subsets of proteins differently affected by radiation depending on the resveratrol context. The first subset (84 differentially expressed proteins; DEPs) represented proteins influenced by radiation in all resveratrol pretreatment regimens. The second subset (228 DEPs), linked to DNA repair, cell cycle checkpoints, and apoptosis, was affected by radiation only in the absence of resveratrol preconditioning, indicating the compound’s protective effect. The third subset (252 DEPs) involved in metabolism regulation appeared only after extended resveratrol preconditioning. In conclusion, the results demonstrate that hypothetical time-dependent cardioprotective effects of resveratrol are linked to significant proteomic reprogramming of cardiomyocytes caused by long-term pretreatment.