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Proteomic profiles in cardiomyocytes exposed to ionizing radiation and resveratrol: potential radioprotective mechanisms of the different resveratrol pretreatment regimens

ABSTRACT: Resveratrol, a plant-derived antioxidant, may protect against radiation by modulating cellular metabolism and 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 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, 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 represented the core cellular response to radiation, unaffected by resveratrol. The second, 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 involved in metabolism regulation was affected by radiation only after extended resveratrol preconditioning. In conclusion, our data documented that the radioprotective effects of resveratrol are linked to a proteomic reprogramming of cardiomyocytes following prolonged exposure.

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ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Monika Pietrowska

LAB HEAD: Monika Pietrowska

PROVIDER: PXD069084 | Pride | 2025-11-10

REPOSITORIES: Pride

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

Gramatyka Michalina M Gawin Marta M Kurczyk Agata A Gądek Adam A Pietrowska Monika M Widłak Piotr P

International journal of molecular sciences 20251021 20

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 partial ...[more]

PMID: 41155513

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Project description:The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to downregulate NF-κB; a major contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the observed effects. The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, actual skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting. Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways (e.g.IL-17A, IL-17F,IL-23p19 ). Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis. In conclusion, resveratrol ameliorates psoriasis, and changes in expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner suggests it might have a role in the treatment of psoriasis and should be explored further in a human setting.

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