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SHR Neuro Cancer Cardio Lipid Metab Microb

Dostál, Z; Zholobenko, AV; Přichystalová, H; Gottschalk, B; Valentová, K; Malli, R; Modrianský, M.
Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular Ca²⁺ elevations and mitochondrial depolarisation.
Biochem Pharmacol. 2024; 222:116094 Doi: 10.1016/j.bcp.2024.116094
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Co-authors Med Uni Graz

Gottschalk Benjamin

Malli Roland

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Abstract:

BACKGROUND AND AIM: Osmotic changes represent a burden for the body and their limitation would be beneficial. We hypothesized that ubiquitous natural compounds could guard against cytotoxic effects of osmotic stress. We evaluated the anti-hypertonic mechanism of quercetin and 2,3-dehydrosilybin in H9c2 cells in vitro. EXPERIMENTAL PROCEDURE: Protective effect of both compounds was determined by neutral red assay, cell apoptosis was estimated by measuring caspase-3 activity and verified by western blot and annexin V assay. Phosphorylation level of selected proteins was also detected. Mitochondrial membrane potential was evaluated using dye JC-1. Ca²⁺ signals were evaluated using genetically encoded fluorescent Ca²⁺ biosensor GCaMP7f. Formation of reactive oxygen species was measured using an oxidant-sensing probe dihydrofluorescein diacetate. KEY RESULTS: Quercetin protected H9c2 cells against hypertonic stress-induced cell death. We observed a significant increase in intracellular Ca²⁺ levels ([Ca²⁺]_cyto) when cells originally placed in a hypertonic solution were returned to a normotonic environment. Quercetin was found to prevent this increase in [Ca²⁺]_cyto and also the depolarization of mitochondrial membrane potential. CONCLUSIONS AND IMPLICATIONS: Quercetin, but not 2,3-dehydrosilybin, reduced adverse effects of osmotic stress mainly by dampening the elevation of [Ca²⁺]_cyto and mitochondrial Ca²⁺ overload. This may consequently prevent MPTP pore opening and activation of apoptosis.

Find related publications in this database (using NLM MeSH Indexing)

Quercetin - pharmacology

Reactive Oxygen Species - metabolism

Apoptosis - administration & dosage

Cell Death - administration & dosage

Mitochondria - metabolism

Membrane Potential, Mitochondrial - administration & dosage

Oxidative Stress - administration & dosage

Find related publications in this database (Keywords)

Hypertonic stress

Quercetin

2,3-dehydrosilybin

H9c2 cells

Calcium

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