Opposing roles for caspase and calpain death proteases in l-glutamate-induced oxidative neurotoxicity

Elphick, Lucy M.; Hawat, Mohammad; Toms, Nick J.; Meinander, Annika; Mikhailov, Andrey; Eriksson, John E.; Kass, George E.N.

doi:10.1016/j.taap.2008.07.008

Cited by 24 publications

(13 citation statements)

References 62 publications

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“…As shown in Figure 2A, the exposure of cells to 10 mmol/L Glu resulted in chromatin condensation but not DNA fragmentation. A similar form of chromatin condensation has recently been observed in HT22 cells and cerebellar granule neurons exposed to Glu [24,25] . Pretreatment with AA alleviated Glu-induced nuclear morphological alterations.…”

Section: Discussionsupporting

confidence: 79%

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

et al. 2012

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Aim: To investigate whether asiatic acid (AA), a pentacyclic triterpene in Centella asiatica, exerted neuroprotective effects in vitro and in vivo, and to determine the underlying mechanisms. Methods: human neuroblastoma Sh-SY5Y cells were used for in vitro study. Cell viability was determined with the MTT assay. hoechst 33342 staining and flow cytometry were used to examine the apoptosis. The mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were measured using fluorescent dye. PGC-1α and Sirt1 levels were examined using Western blotting. Neonatal mice were given monosodium glutamate (2.5 mg/g) subcutaneously at the neck from postnatal day (PD) 7 to 13, and orally administered with AA on PD 14 daily for 30 d. The learning and memory of the mice were evaluated with the Morris water maze test. hE staining was used to analyze the pyramidal layer structure in the CA1 and CA3 regions. Results: Pretreatment of Sh-SY5Y cells with AA (0.1-100 nmol/L) attenuated toxicity induced by 10 mmol/L glutamate in a concentration-dependent manner. AA 10 nmol/L significantly decreased apoptotic cell death and reduced reactive oxygen species (ROS), stabilized the mitochondrial membrane potential (MMP), and promoted the expression of PGC-1α and Sirt1. In the mice models, oral administration of AA (100 mg/kg) significantly attenuated cognitive deficits in the Morris water maze test, and restored lipid peroxidation and glutathione and the activity of SOD in the hippocampus and cortex to the control levels. AA (50 and 100 mg/kg) also attenuated neuronal damage of the pyramidal layer in the CA1 and CA3 regions. Conclusion: AA attenuates glutamate-induced cognitive deficits of mice and protects SH-SY5Y cells against glutamate-induced apoptosis in vitro.

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Section: Discussionsupporting

confidence: 79%

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

et al. 2012

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“…When we treated glutamate alone in primary cortical neuronal cells, our previous results are consistent with general glutamate-induced toxicity [ 20 33 ]. The active form of calpain 1 (~75 kDa) was clearly observed following exposure to glutamate and activation of this protease was confirmed by α-fordrin cleavage (~150 kDa).…”

Section: Discussionsupporting

confidence: 78%

A single fraction fromUncaria sinensisexerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons

2015

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We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury.

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“…This “active” form of excitotoxic necrosis may be found in vivo, insofar as we reported caspase‐3 activation in morphologically necrotic cells following lithium‐pilocarpine‐induced seizures (Niquet et al, 2007). This mechanism may not be universal, in that cell death with apoptotic features has been reported in a kainate model of seizures (Pollard et al, 1994), and caspase inhibition exacerbates glutamate‐induced oxidative neuronal damage in cell line culture (Elphick et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Contribution of a mitochondrial pathway to excitotoxic neuronal necrosis

Seo

López‐Meraz

Allen

et al. 2009

J of Neuroscience Research

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It is traditionally thought that excitotoxic necrosis is a passive mechanism that does not require the activation of a cell death program. In this study, we examined the contribution of the cytochrome c-dependent mitochondrial death pathway to excitotoxic neuronal necrosis, induced by exposing cultured cortical neurons to 1 mM glutamate for 6 hrs and blocked by the NMDA antagonist, dizocilpine. Glutamate treatment induced early cytochrome c release, followed by activation of caspase-9 and caspase-3. Preincubation with the caspase-9 inhibitor z-LEHD-fmk, the caspase-3 inhibitor z-DEVD-fmk or the specific pan-caspase inhibitor Q-VD-oph decreased the percentage of propidium iodide-positive neurons (52.5 ± 3.1%, 39.4 ± 3.5%, 44.6 ± 3% respectively vs 65 ± 3% in glutamate + vehicle). EM studies showed mitochondrial release of cytochrome c in neurons in the early stages of necrosis, and cleaved caspase-3 immunoreactivity in morphologically necrotic neurons. These results suggest that an active mechanism contributes to the demise of a subpopulation of excitotoxic necrotic neurons.

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Opposing roles for caspase and calpain death proteases in l-glutamate-induced oxidative neurotoxicity

Cited by 24 publications

References 62 publications

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

A single fraction fromUncaria sinensisexerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons

Contribution of a mitochondrial pathway to excitotoxic neuronal necrosis

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