Anti-inflammatory mechanism of taurine against ischemic stroke is related to down-regulation of PARP and NF-κB
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Abstract
Taurine is reported to reduce tissue damage induced by inflammation and to protect the brain against experimental stroke. The objective of this study was to investigate whether taurine reduced ischemic brain damage through suppressing inflammation related to poly (ADP-ribose) polymerase (PARP) and nuclear factor-kappaB (NF-κB) in a rat model of stroke. Rats received 2 h ischemia by intraluminal filament and were then reperfused. Taurine (50 mg/kg) was administered intravenously 1 h after ischemia. Treatment with taurine markedly reduced neurological deficits, lessened brain swelling, attenuated cell death, and decreased the infarct volume 72 h after ischemia. Our data showed the up-regulation of PARP and NF-κB p65 in cytosolic fractions in the core and nuclear fractions in the penumbra and core, and the increases in the nuclear poly (ADP-ribose) levels and the decreases in the intracellular NAD+ levels in the penumbra and core at 22 h of reperfusion; these changes were reversed by taurine. Moreover, taurine significantly reduced the levels of tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase, and intracellular adhesion molecule-1, lessened the activities of myeloperoxidase and attenuated the infiltration of neutrophils in the penumbra and core at 22 h of reperfusion. These data demonstrate that suppressing the inflammatory reaction related to PARP and NF-κB-driven expression of inflammatory mediators may be one mechanism of taurine against ischemic stroke.
Keywords
Experimental stroke Taurine PARP NF-κB InflammationAbbreviations
- DTT
Dithiothreitol
- EDTA
Ethylenediaminetetraacetic acid
- EGTA
Ethyleneglycol bis(2-aminoethyl ether)tetraacetic acid
- HE staining
Hematoxylin and eosin staining
- HEPES
N-2-Hydroxyethylpiperazine-N′-2′-ethanesulfonic acid
- HOCl
Hypochlorous acid
- IκB
Inhibitory κB
- ICAM-1
Intracellular adhesion molecule-1
- IL-1β
Interleukin-1β
- iNOS
Inducible nitric oxide synthase
- MCAo
Middle cerebral artery occlusion
- MPO
Myeloperoxidase
- NAD+
Nicotinamide adenine dinucleotide
- NBT/BCIP
Nitroblue tetrazolium/5-bromo-4-chloro-3-inoloyl-phosphate
- NF-κB
Nuclear factor-kappaB
- PAR
Poly (ADP-ribose)
- PARP
Poly (ADP-ribose) polymerase
- PMSF
Phenylmethanesulfonyl fluoride
- ROS
Reactive oxygen species
- SDS-PAGE
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- Tau-NHCl
Taurine monochloramine
- Tau-NCl2
Taurine dichloramine
- TNF-α
Tumor necrosis factor-α
- TTC
2,3,5-Triphenyltetrazolium chlorides
Notes
Acknowledgments
This research was supported by the Beijing Natural Science Foundation (No. 7052018).
Conflict of interest
The authors declare that they have no conflict of interest.
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