Dataset Information

Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.

ABSTRACT: Tumour cells modify their cellular metabolism with the aim to sustain uncontrolled proliferation. Cancer cells necessitate adequate amounts of NAD and NADPH to support several enzymes that are usually overexpressed and/or overactivated. Nicotinamide adenine dinucleotide (NAD) is an essential cofactor and substrate of several NAD-consuming enzymes, such as PARPs and sirtuins, while NADPH is important in the regulation of the redox status in cells. The present review explores the rationale for targeting the key enzymes that maintain the cellular NAD/NADPH pool in colorectal cancer and the enzymes that consume or use NADP(H).

SUBMITTER: Colombo G

PROVIDER: S-EPMC8645963 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.

Colombo Giorgia G Gelardi Edoardo Luigi Maria ELM Balestrero Federica Carolina FC Moro Marianna M Travelli Cristina C Genazzani Armando A AA

Frontiers in pharmacology 20211122

Tumour cells modify their cellular metabolism with the aim to sustain uncontrolled proliferation. <i>Cancer</i> cells necessitate adequate amounts of NAD and NADPH to support several enzymes that are usually overexpressed and/or overactivated. Nicotinamide adenine dinucleotide (NAD) is an essential cofactor and substrate of several NAD-consuming enzymes, such as PARPs and sirtuins, while NADPH is important in the regulation of the redox status in cells. The present review explores the rationale ...[more]

PMID: 34880756

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Project description:ObjectiveMetabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).MethodsThis was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.Results17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log2 fold change (FC)=1.15, p=0.02) and uracil (log2FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log2FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log2FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD+) (log2FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log2FC=1.17, p=0.02) and cystine (log2FC=1.04, p=0.03) compared with control sera.ConclusionsMetabolites associated with the NAD+ pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.

Dataset Information

Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.

Publications

Insight Into Nicotinamide Adenine Dinucleotide Homeostasis as a Targetable Metabolic Pathway in Colorectal Cancer.

Similar Datasets

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