EMAIL THIS PAGE TO A FRIEND

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke.


PMID 26058697

Abstract

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD(+)/NADH ratio. In this study, we investigated whether mitochondrial NAD(+)-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD(+)-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1405562
Anti-CAT antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2105074
Anti-CAT antibody produced in rabbit, affinity isolated antibody
SAB4503383
Anti-Catalase antibody produced in rabbit, affinity isolated antibody
AV32388
Anti-SIRT3 (AB2) antibody produced in rabbit, IgG fraction of antiserum
SAB3500494
Anti-SIRT3 antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB2502006
Anti-Sirt3 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2500945
Anti-SIRT3 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
S4072
Anti-Sirt3 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA026809
Anti-SIRT3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2501675
Anti-SOD2 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2501676
Anti-SOD2 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1406465
Anti-SOD2 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2701618
Anti-sod2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2701761
Anti-sod2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA001814
Anti-SOD2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2102261
Anti-SOD2 antibody produced in rabbit, affinity isolated antibody
AV35122
Anti-VDAC1 antibody produced in rabbit, IgG fraction of antiserum
N8285
β-Nicotinamide adenine dinucleotide, pkg of 10 mg (per vial)
C21H27N7O14P2
N8410
β-Nicotinamide adenine dinucleotide, pkg of 20 mg (per vial)
C21H27N7O14P2
N8535
β-Nicotinamide adenine dinucleotide, pkg of 50 mg (per vial)
C21H27N7O14P2
N7004
β-Nicotinamide adenine dinucleotide hydrate, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast
C21H27N7O14P2 · xH2O
N6522
β-Nicotinamide adenine dinucleotide hydrate, ≥98%, BioUltra, from yeast
C21H27N7O14P2 · xH2O
N1636
β-Nicotinamide adenine dinucleotide hydrate, purified by column chromatography, ≥99%
C21H27N7O14P2 · xH2O
N3014
β-Nicotinamide adenine dinucleotide hydrate, cell culture tested, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast
C21H27N7O14P2 · xH2O
N7381
β-Nicotinamide adenine dinucleotide hydrate, Grade AA-1, ≥95% (HPLC)
C21H27N7O14P2 · xH2O
N1511
β-Nicotinamide adenine dinucleotide hydrate, ≥99%
C21H27N7O14P2 · xH2O
43410
β-Nicotinamide adenine dinucleotide hydrate, ≥95% (HPLC)
C21H27N7O14P2 · xH2O
N7132
β-Nicotinamide adenine dinucleotide lithium salt from Saccharomyces cerevisiae, ≥95%
C21H26LiN7O14P2
SAB1402140
Monoclonal Anti-CAT, (N-terminal) antibody produced in mouse, clone 2G6, purified immunoglobulin, buffered aqueous solution
C0979
Monoclonal Anti-Catalase antibody produced in mouse, ~2 mg/mL, clone CAT-505, purified immunoglobulin, buffered aqueous solution