Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide).

Autor:	Zeidler JD; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Chini CCS; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Kanamori KS; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Kashyap S; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Espindola-Netto JM; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Thompson K; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Warner G; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Cabral FS; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Peclat TR; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Gomez LS; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA., Lopez SA; Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA., Wandersee MK; Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA., Schoon RA; Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA., Reid K; Interdisciplinary School of Health of Sciences, University Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada., Menzies K; Interdisciplinary School of Health of Sciences, University Ottawa Brain and Mind Research Institute, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada., Beckedorff F; Sylvester Comprehensive Cancer Center, Department of Human Genetics, Biomedical Research Building, University of Miami Miller School of Medicine, Miami, FL 33136, USA., Reid JM; Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA., Brachs S; Charité - Universitätsmedizin Berlin, Department of Endocrinology and Metabolism, 10115 Berlin, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany., Meyer RG; Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA., Meyer-Ficca ML; Department of Animal, Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, School of Veterinary Medicine, Utah State University, Logan, UT 84332, USA., Chini EN; Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.; Department of Anesthesiology and Perioperative Medicine Mayo Clinic, Jacksonville, FL 32224, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Oct 23; Vol. 25 (11), pp. 105431. Date of Electronic Publication: 2022 Oct 23 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105431
Abstrakt:	In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B 3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels. Competing Interests: E.N.C. holds a patent on the use of CD38 inhibitors for metabolic diseases licensed by Elysium health. E.N.C. is a consultant for TeneoBio, Calico, Mitobridge, and Cytokinetics. E.N.C. is on the advisory board of Eolo Pharma. E.N.C. own stocks in TeneoBio. Research in the E.N.C. laboratory has been conducted in compliance with Mayo Clinic’s conflict of interest policies. (© 2022 The Author(s).)
Databáze:	MEDLINE
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