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eng
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Description
NAD plays critical roles in various biological processes through the function of SIRT1. Although classical studies in
mammals showed that nicotinic acid (NA) is a better precursor than nicotinamide (Nam) in elevating tissue NAD levels, molecular details ofNADsynthesis fromNAremain largely unknown. We here identified NA phosphoribosyltransferase (NAPRT) in humans and provided direct evidence of tight link between NAPRTand the increase in cellularNADlevels. The enzyme was abundantly expressed in the small intestine, liver, and kidney in mice and mediated [14C]NAD synthesis from [14C]NA in human cells. In cells expressing endogenous NAPRT, the addition of
NA but not Nam almost doubled cellular NAD contents and decreased cytotoxicity by H2O2. Both effects were reversed by knockdown of NAPRT expression. These results indicate that NAPRT is essential for NA to increase cellular NAD levels and, thus, to prevent oxidative stress of the cells. Kinetic analyses revealed that NAPRT, but not Nam phosphoribosyltransferase (NamPRT, also known as pre-B-cell colony-enhancing factor or visfatin), is insensitive to the physiological concentration of NAD. Together, we conclude thatNAelevates cellularNADlevels throughNAPRTfunction and, thus, protects the cells against stress, partly due to lack of feedback inhibition of NAPRT but not Nam phosphoribosyltransferase by NAD. The ability of NA to increase cellular NAD contents may account for some of the
clinically observed effects of the vitamin and further implies a novel application of the vitamin to treat diseases such as those associated with the depletion of cellular NAD pools.
Journal Title
The Journal of Biological Chemistry
Volume
282
Issue
34
Start Page
24574
End Page
24582
sort
24574
ISSN
0021-9258
ISSN(Online)
1083-351X
Published Date
2007
DOI
PubMed ID
Publisher
Baltimore, MD : American Society for Biochemistry and Molecular Biology
NII Type
Journal Article
Content Type
9001
Rights
Reuse of JBC content must include the following: This research was originally published in the Journal of Biological Chemistry. Author(s). Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem.2007 Aug 24;282(34):24574-82. doi: 10.1074/jbc.M610357200. Epub 2007 Jun 29. (c) the American Society for Biochemistry and Molecular Biology or (c) the Authors.
Text Version
著者版
Gyoseki ID
e5737
OAI-PMH Set
Faculty of Medicine
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