HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 34, 24574-24582, August 24, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/34/24574    most recent M610357200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hara, N. Articles by Tsuchiya, M. Search for Related Content PubMed PubMed Citation Articles by Hara, N. Articles by Tsuchiya, M. Social Bookmarking                      What's this?

Elevation of Cellular NAD Levels by Nicotinic Acid and Involvement of Nicotinic Acid Phosphoribosyltransferase in Human Cells^*

Nobumasa Hara¹, Kazuo Yamada, Tomoko Shibata, Harumi Osago, Tatsuya Hashimoto, and Mikako Tsuchiya

From the Department of Biochemistry and Center for Integrated Research in Science, Shimane University Faculty of Medicine, 89-1, Izumo, Shimane 693-8501, Japan

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 of NAD synthesis from NA remain largely unknown. We here identified NA phosphoribosyltransferase (NAPRT) in humans and provided direct evidence of tight link between NAPRT and the increase in cellular NAD levels. 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 that NA elevates cellular NAD levels through NAPRT function and, thus, protects the cells against stress, partly due to lack of feedback inhibition of NAPRT but not NamPRT 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.

Received for publication, November 7, 2006 , and in revised form, June 28, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental methods and Figs. 1 and 2.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AB242230 [GenBank] .

¹ To whom correspondence should be addressed. Tel.: 81-853-20-2120; Fax: 81-853-20-2120; E-mail: nhara{at}med.shimane-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Koch-Nolte, F. Haag, A. H. Guse, F. Lund, and M. Ziegler Emerging Roles of NAD+ and Its Metabolites in Cell Signaling Sci. Signal., February 10, 2009; 2(57): mr1 - mr1. [Abstract] [Full Text] [PDF]

				A. Bahn, Y. Hagos, S. Reuter, D. Balen, H. Brzica, W. Krick, B. C. Burckhardt, I. Sabolic, and G. Burckhardt Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13) J. Biol. Chem., June 13, 2008; 283(24): 16332 - 16341. [Abstract] [Full Text] [PDF]

				T. Luk, Z. Malam, and J. C. Marshall Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity J. Leukoc. Biol., April 1, 2008; 83(4): 804 - 816. [Abstract] [Full Text] [PDF]