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

被引：5

作者：

Zeidler, Julianna D. ^{[1
,2
]}

Chini, Claudia C. S. ^{[1
,2
]}

Kanamori, Karina S. ^{[1
,2
]}

Kashyap, Sonu ^{[1
,2
]}

Espindola-Netto, Jair M. ^{[1
,2
]}

Thompson, Katie ^{[1
,2
]}

Warner, Gina ^{[1
,2
]}

Cabral, Fernanda S. ^{[1
,2
]}

Peclat, Thais R. ^{[1
,2
]}

Gomez, Lilian Sales ^{[1
,2
]}

Lopez, Sierra A. ^{[1
,3
]}

Wandersee, Miles K. ^{[1
,3
]}

Schoon, Renee A. ^{[1
,4
]}

Reid, Kimberly ^{[1
,5
]}

Menzies, Keir ^{[1
,5
]}

Beckedorff, Felipe ^{[1
,6
]}

Reid, Joel M. ^{[1
,4
]}

Brachs, Sebastian ^{[1
,7
,8
]}

Meyer, Ralph G. ^{[1
,3
]}

Meyer-Ficca, Mirella L. ^{[1
,3
]}

Chini, Eduardo Nunes ^{[1
,2
]}

机构：

[1] Mayo Clin Coll Med, Kogod Aging Ctr, Dept Anesthesiol & Perioperat Med, Signal Transduct & Mol Nutr Lab, Rochester, MN 55905 USA

[2] Perioperat Med Mayo Clin, Dept Anesthesiol, Jacksonville, FL 32224 USA

[3] Utah State Univ, Coll Agr & Appl Sci, Sch Vet Med, Dept Anim, Logan, UT 84332 USA

[4] Mayo Clin Coll Med, Oncol Res, Rochester, MN 55905 USA

[5] Univ Ottawa Brain, Mind Res Inst, Interdisciplinary Sch Hlth Sci, 451 Smyth Rd, Ottawa, ON 185, Canada

[6] Univ Miami Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Human Genet, Biomed Res Bldg, Miami, FL 33136 USA

[7] Charite, Dept Endocrinol & Metab, D-10115 Berlin, Germany

[8] German Ctr Cardiovasc Res, DZHK, Partner Site Berlin, Berlin, Germany

来源：

ISCIENCE | 2022年 / 25卷 / 11期

基金：

美国国家卫生研究院;

关键词：

MHC CLASS-II; TRANSGENIC MICE; EXPRESSION; NAD; INHIBITION; CD38; ENZYME; PHOSPHORIBOSYLTRANSFERASE; DECARBOXYLASE; ACTIVATION;

D O I：

10.1016/j.isci.2022.105431

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 the 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.

引用

页数：24

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