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Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells.

ABSTRACT: Nicotinamide riboside (NR), a NAD⁺ precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD⁺ availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD⁺ increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.

SUBMITTER: Cordeiro EWF

PROVIDER: S-EPMC11337214 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells.

Cordeiro Everson Willian Fialho EWF Marzola Elisabete Leide EL Maekawa Ricardo Soei RS Santos Matheus Relvas Dos MRD Assunção Lucas Gade LG Massafera Mariana Pereira MP Oliveira Joseana de J Batista Thainá Gomes Cury TGC Sales Maria Cármen Oliveira Pinho de MCOP Maria-Engler Silvya Stuchi SS Di Mascio Paolo P Medeiros Marisa Helena Gennari de MHG Ronsein Graziella Eliza GE Loureiro Ana Paula de Melo APM

Chemical research in toxicology 20240711 8

Nicotinamide riboside (NR), a NAD<sup>+</sup> precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD<sup>+</sup> availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolaye ...[more]

PMID: 38990804

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Project description:Folate (vitamin B9) and its biologically active derivatives are well-known antioxidant molecules protecting cells from oxidative degradation. The presence of high glucose, often found in diabetic patients, causes oxidative stress resulting in cellular stress and inflammatory injury. Cells in organs such as the lung are highly prone to inflammation, and various protective mechanisms exist to prevent the progressive disorders arising from inflammation. In the present study, the synthetic form of folate, i.e. folic acid, and active forms of folate, i.e. 5-methyltetrahydrofolate and 10-formyltetrahydrofolate, were evaluated for their antioxidant and antiinflammatory potential against high glucose (50 mM)-mediated oxidative stress and inflammation in BEAS-2B cells, an immortalised bronchial epithelial cell line. High glucose treatment showed a 67% reduction in the viability of BEAS-2B cells, which was restored to the viability levels seen in control cultures by the addition of active folate derivatives to the culture media. The DCFH-DA fluorometric assay was performed for oxidative stress detection. The high glucose-treated cells showed a significantly higher fluorescence intensity (1.81- and 3.8-fold for microplate assay and microscopic observation, respectively), which was normalised to control levels on supplementation with active folate derivatives. The proinflammatory NF-κB p50 protein expression in the active folate derivative-supplemented high glucose-treated cells was significantly lower compared to the folic acid treatment. In support of these findings, in silico microarray GENVESTIGATOR database analysis showed that in bronchiolar small airway epithelial cells exposed to inflammatory condition, folate utilization pathway genes are largely downregulated. However, the folate-binding protein gene, which encodes to the folate receptor 1 (FOLR1), is significantly upregulated, suggesting a high demand for folate by these cells in inflammatory situations. Supplementation of the active folate derivatives 5-methyltetrahydrofolate and 10-formyltetrahydrofolate resulted in significantly higher protection over the folic acid from high glucose-induced oxidative stress and inflammation. Therefore, the biologically active folate derivatives could be a suitable alternative over the folic acid for alleviating inflammatory injury-causing oxidative stress.

Dataset Information

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells.

Publications

Nicotinamide riboside Induced Energy Stress and Metabolic Reprogramming in BEAS-2B Cells.

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