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

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Cordeiro, Everson Willian Fialho ; Marzola, Elisabete Leide ; Maekawa, Ricardo Soei ; dos Santos, Matheus Relvas ; Assuncao, Lucas Gade ; Massafera, Mariana Pereira ; de Oliveira, Joseana ; Batista, Thaina Gomes Cury ; de Sales, Maria Carmen Oliveira Pinho ; Maria-Engler, Silvya Stuchi ; Di Mascio, Paolo ; de Medeiros, Marisa Helena Gennari ; Ronsein, Graziella Eliza ; Loureiro, Ana Paula de Melo

• Document type: Journal article
• Source: Chemical Research in Toxicology; v. 37, n. 8, p. 23-pg., 2024-07-11.

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 mu M) 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 mu M 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 mu M 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. (AU)

• FAPESP's process: 16/20925-7 - Modulation of DNA adducts, metabolism, and epigenetic marks in cultured normal human cells supplemented with benz[a]pyrene, NAD+, succinate and/or fumarate: implications to tumorigenesis
• Grantee: Ana Paula de Melo Loureiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/08784-9 - Modulation of NAD+ intracellular concentration and its effect in the tumorigenesis induced by benzo[a]pyrene in human bronchial epithelial cells
• Grantee: Everson Willian Fialho Cordeiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)