BRENDA - Enzyme Database show

Extension of human cell lifespan by nicotinamide phosphoribosyltransferase

van der Veer, E.; Ho, C.; ONeil, C.; Barbosa, N.; Scott, R.; Cregan, S.P.; Pickering, J.G.; J. Biol. Chem. 282, 10841-10845 (2007)

Data extracted from this reference:

Application
EC Number
Application
Commentary
Organism
2.4.2.12
medicine
longevity enzyme for human SMCs
Homo sapiens
Cloned(Commentary)
EC Number
Commentary
Organism
2.4.2.12
a retroviral gene delivery system is used to generate human cells stably overexpressing Nampt. Introducing the Nampt gene into aging human SMCs delays senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress; in pQCXIP-IHRES-PURO for retroviral delivery and stable overexpression in Phoenix-amphotropic retrovirus packaging cell line
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.2.12
FK866
Nampt antagonist, 10 nM, reduction of Nampt activity in SMCs to 22 +/-2% of baseline activity accompanied with shortened senescent-free survival; reducing Nampt activity with the antagonist FK866 induces premature senescence in smooth muscle cells
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.4.2.12
additional information
Homo sapiens
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
?
-
-
-
2.4.2.12
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
-
nicotinamide mononucleotide + diphosphate
-
-
r
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.4.2.12
Homo sapiens
-
-
-
2.4.2.12
Homo sapiens
P43490
-
-
Source Tissue
EC Number
Source Tissue
Commentary
Organism
Textmining
2.4.2.12
aorta thoracica smooth muscle
primary SMC culture, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody; primary SMC culture stably expressing Nampt, 2.1 +/-0.3 additional population doublings constituting 34 +/-4% lifespan prolongation
Homo sapiens
-
2.4.2.12
HITC6 cell
SMC clonal line, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody, 14 +/-3% of basal Nampt activity in presenescent SMC, direct relationship between Nampt activity and number of replication cycles preceeding senescence; SMC clonal line stably expressing Nampt, 7.1 +/-3.1 fold higher Nampt activity, 6.3 +/-0.3 additional population doublings constituting 71 +/-7% lifespan prolongation, 19 +/-2% reduction in number of senescent cells at passage 37 compared to control HITC6 cells is dependent on SIRT1 activity and associated with increased p53 degradation and protection against oxidative cell damage as response to 150 microM hydrogen peroxide
Homo sapiens
-
2.4.2.12
skin fibroblast
from individual with Hutchison-Gilford progeria syndrome associated with premature atherosclerosis, cell lifespan extension upon Nampt overexpression
Homo sapiens
-
2.4.2.12
vascular smooth muscle cell
-
Homo sapiens
-
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.2.12
additional information
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
680749
Homo sapiens
?
-
-
-
-
2.4.2.12
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
-
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
r
2.4.2.12
nictoinamide + alpha-D-5-phosphoribosyl 1-diphosphate
whole cell lysates incubated with 5 microM [carbonyl-14C]nicotinamide + 0.5 mM alpha-D-5-phosphoribosyl-1-diphosphate at pH 8.8
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
produced NMN quantified by scintillation counting
-
-
r
Application (protein specific)
EC Number
Application
Commentary
Organism
2.4.2.12
medicine
longevity enzyme for human SMCs
Homo sapiens
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
2.4.2.12
a retroviral gene delivery system is used to generate human cells stably overexpressing Nampt. Introducing the Nampt gene into aging human SMCs delays senescence and substantially lengthened cell lifespan, together with enhanced resistance to oxidative stress
Homo sapiens
2.4.2.12
in pQCXIP-IHRES-PURO for retroviral delivery and stable overexpression in Phoenix-amphotropic retrovirus packaging cell line
Homo sapiens
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.4.2.12
FK866
reducing Nampt activity with the antagonist FK866 induces premature senescence in smooth muscle cells
Homo sapiens
2.4.2.12
FK866
Nampt antagonist, 10 nM, reduction of Nampt activity in SMCs to 22 +/-2% of baseline activity accompanied with shortened senescent-free survival
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.4.2.12
additional information
Homo sapiens
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
?
-
-
-
2.4.2.12
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
Homo sapiens
-
nicotinamide mononucleotide + diphosphate
-
-
r
Source Tissue (protein specific)
EC Number
Source Tissue
Commentary
Organism
Textmining
2.4.2.12
aorta thoracica smooth muscle
primary SMC culture, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody; primary SMC culture stably expressing Nampt, 2.1 +/-0.3 additional population doublings constituting 34 +/-4% lifespan prolongation
Homo sapiens
-
2.4.2.12
HITC6 cell
SMC clonal line, Nampt expression declines as SMC approach senescence as detected by immunoblotting using rabbit-polyclonal anti-human Nampt/Pre-B-cell colony-enhancing factor antibody, 14 +/-3% of basal Nampt activity in presenescent SMC, direct relationship between Nampt activity and number of replication cycles preceeding senescence; SMC clonal line stably expressing Nampt, 7.1 +/-3.1 fold higher Nampt activity, 6.3 +/-0.3 additional population doublings constituting 71 +/-7% lifespan prolongation, 19 +/-2% reduction in number of senescent cells at passage 37 compared to control HITC6 cells is dependent on SIRT1 activity and associated with increased p53 degradation and protection against oxidative cell damage as response to 150 microM hydrogen peroxide
Homo sapiens
-
2.4.2.12
skin fibroblast
from individual with Hutchison-Gilford progeria syndrome associated with premature atherosclerosis, cell lifespan extension upon Nampt overexpression
Homo sapiens
-
2.4.2.12
vascular smooth muscle cell
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.4.2.12
additional information
rate-limiting enzyme for NAD+ salvage from nicotinamide. Replicative senescence of smooth muscle cells is preceded by a marked decline in the expression and activity of Nampt. Nampt is a longevity protein that can add stress-resistant life to human smooth muscle cells by optimizing SIRT1-mediated p53 degradation
680749
Homo sapiens
?
-
-
-
-
2.4.2.12
nicotinamide + alpha-D-5-phosphoribosyl 1-diphosphate
-
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
-
-
-
r
2.4.2.12
nictoinamide + alpha-D-5-phosphoribosyl 1-diphosphate
whole cell lysates incubated with 5 microM [carbonyl-14C]nicotinamide + 0.5 mM alpha-D-5-phosphoribosyl-1-diphosphate at pH 8.8
680749
Homo sapiens
nicotinamide mononucleotide + diphosphate
produced NMN quantified by scintillation counting
-
-
r