Limits...
Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.

Cao Y, Gao Y, Xu S, Bao J, Lin Y, Luo X, Wang Y, Luo Q, Jiang J, Neale JH, Zhong C - BMC Neurosci (2016)

Bottom Line: Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury.Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde.These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

ABSTRACT

Background: Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system.

Results: Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice.

Conclusions: These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Effects of GCP II KO on GSH (a), MDA (b), SOD (c), GPx (d). TBI caused significant decreases of GSH level, SOD, GPx activities, and an increase in the MDA level. GCP II KO significantly moderated these changes while not altering the levels in sham controls. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured WT mice
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4836105&req=5

Fig1: Effects of GCP II KO on GSH (a), MDA (b), SOD (c), GPx (d). TBI caused significant decreases of GSH level, SOD, GPx activities, and an increase in the MDA level. GCP II KO significantly moderated these changes while not altering the levels in sham controls. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured WT mice

Mentions: Decreased SOD and GPx activities, GSH level as well as increased MDA level were observed in the WT TBI group compared to the WT sham group (p < 0.05, n = 6) (Fig. 1). No significant differences were observed between the WT and GCPII KO sham group. GCPII KO resulted in significantly diminished elevation of MDA level compared to WT TBI mice (p < 0.05, n = 6). In addition, GCPII deletion produced significant increases in GSH level, and SOD and GPx activities compared to their WT counterparts (all p < 0.05, n = 6).Fig. 1


Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.

Cao Y, Gao Y, Xu S, Bao J, Lin Y, Luo X, Wang Y, Luo Q, Jiang J, Neale JH, Zhong C - BMC Neurosci (2016)

Effects of GCP II KO on GSH (a), MDA (b), SOD (c), GPx (d). TBI caused significant decreases of GSH level, SOD, GPx activities, and an increase in the MDA level. GCP II KO significantly moderated these changes while not altering the levels in sham controls. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured WT mice
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836105&req=5

Fig1: Effects of GCP II KO on GSH (a), MDA (b), SOD (c), GPx (d). TBI caused significant decreases of GSH level, SOD, GPx activities, and an increase in the MDA level. GCP II KO significantly moderated these changes while not altering the levels in sham controls. Data were represented as mean ± SEM (n = 6 per group); *p < 0.05, versus sham control of the same genotype; #p < 0.05, versus injured WT mice
Mentions: Decreased SOD and GPx activities, GSH level as well as increased MDA level were observed in the WT TBI group compared to the WT sham group (p < 0.05, n = 6) (Fig. 1). No significant differences were observed between the WT and GCPII KO sham group. GCPII KO resulted in significantly diminished elevation of MDA level compared to WT TBI mice (p < 0.05, n = 6). In addition, GCPII deletion produced significant increases in GSH level, and SOD and GPx activities compared to their WT counterparts (all p < 0.05, n = 6).Fig. 1

Bottom Line: Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury.Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde.These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

ABSTRACT

Background: Glutamate carboxypeptidase II (GCPII) inactivates the peptide co-transmitter N-acetylaspartylglutamate following synaptic release. Inhibition of GCPII elevates extracellular levels of the peptide, inhibits glutamate release and is neuroprotective in an animal model of traumatic brain injury. GCPII gene knockout mice were used to examine the cellular mechanisms underlying the neuroprotective efficacy of this transmitter system.

Results: Following controlled cortical impact injury, GCPII knockout (KO) mice exhibited reduced TUNEL-positive nuclei in the contusion margin of the cerebral cortex relative to wild type mice. Impact injury reduced glutathione levels and superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde. Each of these effects was moderated in KO mice relative to wild type. Similarly, the injury-induced increases in cleaved caspase-3, cytosolic cytochrome c levels and Bcl-2/Bax ratio observed in wild type mice were attenuated in the knockout mice.

Conclusions: These data support the hypothesis that the neuroprotective efficacy of GCPII KO in traumatic brain injury is mediated via a reduction in oxidative stress.

No MeSH data available.


Related in: MedlinePlus